1932

Abstract

Epidermal growth factor receptor (EGFR) activation impacts the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases including hypertension, cardiac hypertrophy, renal fibrosis, and abdominal aortic aneurysm. The capacity of G protein–coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is called transactivation and is well described, yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight recent advancements in defining the signaling cascades and downstream consequences of EGFR transactivation in the cardiovascular renal system. We also focus on studies that link EGFR transactivation to animal models of the disease, and we discuss potential therapeutic applications.

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2016-01-06
2024-06-14
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Literature Cited

  1. Zeng F, Harris RC. 1.  2014. Epidermal growth factor, from gene organization to bedside. Semin. Cell Dev. Biol. 28:2–11 [Google Scholar]
  2. Yarden Y, Sliwkowski MX. 2.  2001. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell Biol. 2:127–37 [Google Scholar]
  3. Wieduwilt MJ, Moasser MM. 3.  2008. The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol. Life Sci. 65:1566–84 [Google Scholar]
  4. Arteaga CL, Engelman JA. 4.  2014. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 25:282–303 [Google Scholar]
  5. Makki N, Thiel KW, Miller FJ Jr. 5.  2013. The epidermal growth factor receptor and its ligands in cardiovascular disease. Int. J. Mol. Sci. 14:20597–613 [Google Scholar]
  6. Schreier B, Gekle M, Grossmann C. 6.  2014. Role of epidermal growth factor receptor in vascular structure and function. Curr. Opin. Nephrol. Hypertens. 23:113–21 [Google Scholar]
  7. Leserer M, Gschwind A, Ullrich A. 7.  2000. Epidermal growth factor receptor signal transactivation. IUBMB Life 49:405–9 [Google Scholar]
  8. Wetzker R, Bohmer FD. 8.  2003. Transactivation joins multiple tracks to the ERK/MAPK cascade. Nat. Rev. Mol. Cell Biol. 4:651–57 [Google Scholar]
  9. George AJ, Purdue BW, Gould CM, Thomas DW, Handoko Y. 9.  et al. 2013. A functional siRNA screen identifies genes modulating angiotensin II–mediated EGFR transactivation. J. Cell Sci. 126:5377–90 [Google Scholar]
  10. George AJ, Hannan RD, Thomas WG. 10.  2013. Unravelling the molecular complexity of GPCR-mediated EGFR transactivation using functional genomics approaches. FEBS J. 280:5258–68 [Google Scholar]
  11. Ohtsu H, Dempsey PJ, Eguchi S. 11.  2006. ADAMs as mediators of EGF receptor transactivation by G protein–coupled receptors. Am. J. Physiol. Cell Physiol. 291:C1–10 [Google Scholar]
  12. Elliott KJ, Bourne AM, Takayanagi T, Takaguri A, Kobayashi T. 12.  et al. 2013. ADAM17 silencing by adenovirus encoding miRNA-embedded siRNA revealed essential signal transduction by angiotensin II in vascular smooth muscle cells. J. Mol. Cell Cardiol. 62:1–7 [Google Scholar]
  13. Overland AC, Insel PA. 13.  2015. Heterotrimeric G proteins directly regulate MMP14/membrane type-1 matrix metalloprotease: a novel mechanism for GPCR-EGFR transactivation. J. Biol. Chem. 290:9941–47 [Google Scholar]
  14. Ushio-Fukai M, Alexander RW. 14.  2006. Caveolin-dependent angiotensin II type 1 receptor signaling in vascular smooth muscle. Hypertension 48:797–803 [Google Scholar]
  15. Tilley DG. 15.  2011. G protein–dependent and G protein–independent signaling pathways and their impact on cardiac function. Circ. Res. 109:217–30 [Google Scholar]
  16. Blobel CP. 16.  2005. ADAMs: key components in EGFR signalling and development. Nat. Rev. Mol. Cell Biol. 6:32–43 [Google Scholar]
  17. Dreymueller D, Pruessmeyer J, Groth E, Ludwig A. 17.  2012. The role of ADAM-mediated shedding in vascular biology. Eur. J. Cell Biol. 91:472–85 [Google Scholar]
  18. Mehta PK, Griendling KK. 18.  2007. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am. J. Physiol. Cell Physiol. 292:C82–97 [Google Scholar]
  19. Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S. 19.  2007. Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology. Clin. Sci. 112:417–28 [Google Scholar]
  20. Eguchi S, Dempsey PJ, Frank GD, Motley ED, Inagami T. 20.  2001. Activation of MAPKs by angiotensin II in vascular smooth muscle cells: metalloprotease-dependent EGF receptor activation is required for activation of ERK and p38 MAPK but not for JNK. J. Biol. Chem. 276:7957–62 [Google Scholar]
  21. Eguchi S, Numaguchi K, Iwasaki H, Matsumoto T, Yamakawa T. 21.  et al. 1998. Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II–induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J. Biol. Chem. 273:8890–96 [Google Scholar]
  22. Briet M, Schiffrin EL. 22.  2013. Treatment of arterial remodeling in essential hypertension. Curr. Hypertens. Rep. 15:3–9 [Google Scholar]
  23. Mifune M, Ohtsu H, Suzuki H, Frank GD, Inagami T. 23.  et al. 2004. Signal transduction of betacellulin in growth and migration of vascular smooth muscle cells. Am. J. Physiol. Cell Physiol. 287:C807–13 [Google Scholar]
  24. Montezano AC, Nguyen Dinh Cat A, Rios FJ, Touyz RM. 24.  2014. Angiotensin II and vascular injury. Curr. Hypertens. Rep. 16:431 [Google Scholar]
  25. Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK. 25.  2002. Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators. Circ. Res. 91:406–13 [Google Scholar]
  26. Touyz RM, Wu XH, He G, Salomon S, Schiffrin EL. 26.  2002. Increased angiotensin II–mediated Src signaling via epidermal growth factor receptor transactivation is associated with decreased C-terminal Src kinase activity in vascular smooth muscle cells from spontaneously hypertensive rats. Hypertension 39:479–85 [Google Scholar]
  27. Ohtsu H, Higuchi S, Shirai H, Eguchi K, Suzuki H. 27.  et al. 2008. Central role of Gq in the hypertrophic signal transduction of angiotensin II in vascular smooth muscle cells. Endocrinology 149:3569–75 [Google Scholar]
  28. Iwasaki H, Eguchi S, Ueno H, Marumo F, Hirata Y. 28.  1999. Endothelin-mediated vascular growth requires p42/p44 mitogen-activated protein kinase and p70 S6 kinase cascades via transactivation of epidermal growth factor receptor. Endocrinology 140:4659–68 [Google Scholar]
  29. Schreier B, Dohler M, Rabe S, Schneider B, Schwerdt G. 29.  et al. 2011. Consequences of epidermal growth factor receptor (ErbB1) loss for vascular smooth muscle cells from mice with targeted deletion of ErbB1. Arterioscler. Thromb. Vasc. Biol. 31:1643–52 [Google Scholar]
  30. Ohtsu H, Dempsey PJ, Frank GD, Brailoiu E, Higuchi S. 30.  et al. 2006. ADAM17 mediates epidermal growth factor receptor transactivation and vascular smooth muscle cell hypertrophy induced by angiotensin II. Arterioscler. Thromb. Vasc. Biol. 26:e133–37 [Google Scholar]
  31. Li F, Malik KU. 31.  2005. Angiotensin II–induced Akt activation through the epidermal growth factor receptor in vascular smooth muscle cells is mediated by phospholipid metabolites derived by activation of phospholipase D. J. Pharmacol. Exp. Ther. 312:1043–54 [Google Scholar]
  32. Kim J, Ahn S, Rajagopal K, Lefkowitz RJ. 32.  2009. Independent β-arrestin2 and Gq/protein kinase Cζ pathways for ERK stimulated by angiotensin type 1A receptors in vascular smooth muscle cells converge on transactivation of the epidermal growth factor receptor. J. Biol. Chem. 284:11953–62 [Google Scholar]
  33. Abdallah RT, Keum JS, El-Shewy HM, Lee MH, Wang B. 33.  et al. 2010. Plasma kallikrein promotes epidermal growth factor receptor transactivation and signaling in vascular smooth muscle through direct activation of protease-activated receptors. J. Biol. Chem. 285:35206–15 [Google Scholar]
  34. Hao L, Du M, Lopez-Campistrous A, Fernandez-Patron C. 34.  2004. Agonist-induced activation of matrix metalloproteinase-7 promotes vasoconstriction through the epidermal growth factor-receptor pathway. Circ. Res. 94:68–76 [Google Scholar]
  35. Hao L, Nishimura T, Wo H, Fernandez-Patron C. 35.  2006. Vascular responses to α1-adrenergic receptors in small rat mesenteric arteries depend on mitochondrial reactive oxygen species. Arterioscler. Thromb. Vasc. Biol. 26:819–25 [Google Scholar]
  36. Nagareddy PR, Chow FL, Hao L, Wang X, Nishimura T. 36.  et al. 2009. Maintenance of adrenergic vascular tone by MMP transactivation of the EGFR requires PI3K and mitochondrial ATP synthesis. Cardiovasc. Res. 84:368–77 [Google Scholar]
  37. Gratton JP, Bernatchez P, Sessa WC. 37.  2004. Caveolae and caveolins in the cardiovascular system. Circ. Res. 94:1408–17 [Google Scholar]
  38. Takaguri A, Shirai H, Kimura K, Hinoki A, Eguchi K. 38.  et al. 2011. Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II. J. Mol. Cell Cardiol. 50:545–51 [Google Scholar]
  39. Takayanagi T, Crawford KJ, Kobayashi T, Obama T, Tsuji T. 39.  et al. 2014. Caveolin 1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase. Clin. Sci. 126:785–94 [Google Scholar]
  40. Grossmann C, Krug AW, Freudinger R, Mildenberger S, Voelker K, Gekle M. 40.  2007. Aldosterone-induced EGFR expression: interaction between the human mineralocorticoid receptor and the human EGFR promoter. Am. J. Physiol. Endocrinol. Metab. 292:E1790–800 [Google Scholar]
  41. Mazak I, Fiebeler A, Muller DN, Park JK, Shagdarsuren E. 41.  et al. 2004. Aldosterone potentiates angiotensin II–induced signaling in vascular smooth muscle cells. Circulation 109:2792–800 [Google Scholar]
  42. Min LJ, Mogi M, Li JM, Iwanami J, Iwai M, Horiuchi M. 42.  2005. Aldosterone and angiotensin II synergistically induce mitogenic response in vascular smooth muscle cells. Circ. Res. 97:434–42 [Google Scholar]
  43. Montezano AC, Callera GE, Yogi A, He Y, Tostes RC. 43.  et al. 2008. Aldosterone and angiotensin II synergistically stimulate migration in vascular smooth muscle cells through c-Src-regulated redox-sensitive RhoA pathways. Arterioscler. Thromb. Vasc. Biol. 28:1511–18 [Google Scholar]
  44. Meinel S, Gekle M, Grossmann C. 44.  2014. Mineralocorticoid receptor signaling: crosstalk with membrane receptors and other modulators. Steroids 91:3–10 [Google Scholar]
  45. Limor R, Kaplan M, Sharon O, Knoll E, Naidich M. 45.  et al. 2009. Aldosterone up-regulates 12- and 15-lipoxygenase expression and LDL oxidation in human vascular smooth muscle cells. J. Cell Biochem. 108:1203–10 [Google Scholar]
  46. Krug AW, Allenhofer L, Monticone R, Spinetti G, Gekle M. 46.  et al. 2010. Elevated mineralocorticoid receptor activity in aged rat vascular smooth muscle cells promotes a proinflammatory phenotype via extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and epidermal growth factor receptor-dependent pathways. Hypertension 55:1476–83 [Google Scholar]
  47. Frank GD, Mifune M, Inagami T, Ohba M, Sasaki T. 47.  et al. 2003. Distinct mechanisms of receptor and nonreceptor tyrosine kinase activation by reactive oxygen species in vascular smooth muscle cells: role of metalloprotease and protein kinase C-δ. Mol. Cell. Biol. 23:1581–89 [Google Scholar]
  48. Jagadeesha DK, Takapoo M, Banfi B, Bhalla RC, Miller FJ Jr. 48.  2012. Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration. Cardiovasc. Res. 93:406–13 [Google Scholar]
  49. Suc I, Meilhac O, Lajole-Mazenc I, Vandaele J, Jürgens G. 49.  et al. 1998. Activation of EGF receptor by oxidized LDL. FASEB J. 12:665–71 [Google Scholar]
  50. Iwasaki H, Eguchi S, Ueno H, Marumo F, Hirata Y. 50.  2000. Mechanical stretch stimulates growth of vascular smooth muscle cells via epidermal growth factor receptor. Am. J. Physiol. Cell Physiol. 278:H521–29 [Google Scholar]
  51. Konishi A, Berk BC. 51.  2003. Epidermal growth factor receptor transactivation is regulated by glucose in vascular smooth muscle cells. J. Biol. Chem. 278:35049–56 [Google Scholar]
  52. Eguchi S, Frank GD, Mifune M, Inagami T. 52.  2003. Metalloprotease-dependent ErbB ligand shedding in mediating EGFR transactivation and vascular remodelling. Biochem. Soc. Trans. 31:1198–202 [Google Scholar]
  53. Daub H, Weiss FU, Wallasch C, Ullrich A. 53.  1996. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 379:557–60 [Google Scholar]
  54. Jackson LF, Qiu TH, Sunnarborg SW, Chang A, Zhang C. 54.  et al. 2003. Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling. EMBO J. 22:2704–16 [Google Scholar]
  55. Kagiyama S, Eguchi S, Frank GD, Inagami T, Zhang YC, Phillips MI. 55.  2002. Angiotensin II–induced cardiac hypertrophy and hypertension are attenuated by epidermal growth factor receptor antisense. Circulation 106:909–12 [Google Scholar]
  56. Kagiyama S, Qian K, Kagiyama T, Phillips MI. 56.  2003. Antisense to epidermal growth factor receptor prevents the development of left ventricular hypertrophy. Hypertension 41:824–29 [Google Scholar]
  57. Lucchesi PA, Sabri A, Belmadani S, Matrougui K. 57.  2004. Involvement of metalloproteinases 2/9 in epidermal growth factor receptor transactivation in pressure-induced myogenic tone in mouse mesenteric resistance arteries. Circulation 110:3587–93 [Google Scholar]
  58. Nagareddy PR, MacLeod KM, McNeill JH. 58.  2010. GPCR agonist-induced transactivation of the EGFR upregulates MLC II expression and promotes hypertension in insulin-resistant rats. Cardiovasc. Res. 87:177–86 [Google Scholar]
  59. Ulu N, Mulder GM, Vavrinec P, Landheer SW, Duman-Dalkilic B. 59.  et al. 2013. Epidermal growth factor receptor inhibitor PKI-166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5/6 nephrectomized rats. J. Pharmacol. Exp. Ther. 345:393–403 [Google Scholar]
  60. Schreier B, Rabe S, Schneider B, Bretschneider M, Rupp S. 60.  et al. 2013. Loss of epidermal growth factor receptor in vascular smooth muscle cells and cardiomyocytes causes arterial hypotension and cardiac hypertrophy. Hypertension 61:333–40 [Google Scholar]
  61. Takayanagi T, Kawai T, Forrester SJ, Obama T, Tsuji T. 61.  et al. 2015. Role of epidermal growth factor receptor and endoplasmic reticulum stress in vascular remodeling induced by angiotensin II. Hypertension 65:1349–55 [Google Scholar]
  62. Chen J, Chen JK, Nagai K, Plieth D, Tan M. 62.  et al. 2012. EGFR signaling promotes TGFβ-dependent renal fibrosis. J. Am. Soc. Nephrol. 23:215–24 [Google Scholar]
  63. Chan SL, Umesalma S, Baumbach GL. 63.  2015. Epidermal growth factor receptor is critical for angiotensin II–mediated hypertrophy in cerebral arterioles. Hypertension 65:806–12 [Google Scholar]
  64. Obama T, Takayanagi T, Kobayashi T, Bourne AM, Elliott KJ. 64.  et al. 2015. Vascular induction of a disintegrin and metalloprotease 17 by angiotensin II through hypoxia inducible factor 1α. Am. J. Hypertens. 28:10–14 [Google Scholar]
  65. Lundstam U, Hagg U, Sverrisdottir YB, Svensson LE, Gan LM. 65.  2007. Epidermal growth factor levels are related to diastolic blood pressure and carotid artery stiffness. Scand. Cardiovasc. J. 41:308–12 [Google Scholar]
  66. Chan AK, Kalmes A, Hawkins S, Daum G, Clowes AW. 66.  2003. Blockade of the epidermal growth factor receptor decreases intimal hyperplasia in balloon-injured rat carotid artery. J. Vasc. Surg. 37:644–49 [Google Scholar]
  67. Pastore CJ, Isner JM, Bacha PA, Kearney M, Pickering JG. 67.  1995. Epidermal growth factor receptor–targeted cytotoxin inhibits neointimal hyperplasia in vivo. Results of local versus systemic administration. Circ. Res. 77:519–29 [Google Scholar]
  68. Takaguri A, Kimura K, Hinoki A, Bourne AM, Autieri MV, Eguchi S. 68.  2011. A disintegrin and metalloprotease 17 mediates neointimal hyperplasia in vasculature. Hypertension 57:841–45 [Google Scholar]
  69. Zhang H, Sunnarborg SW, McNaughton KK, Johns TG, Lee DC, Faber JE. 69.  2008. Heparin-binding epidermal growth factor-like growth factor signaling in flow-induced arterial remodeling. Circ. Res. 102:1275–85 [Google Scholar]
  70. Stanic B, Pandey D, Fulton DJ, Miller FJ Jr. 70.  2012. Increased epidermal growth factor-like ligands are associated with elevated vascular nicotinamide adenine dinucleotide phosphate oxidase in a primate model of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 32:2452–60 [Google Scholar]
  71. Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA. 71.  2006. The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis. Atherosclerosis 186:38–53 [Google Scholar]
  72. Oksala N, Levula M, Airla N, Pelto-Huikko M, Ortiz RM. 72.  et al. 2009. ADAM-9, ADAM-15, and ADAM-17 are upregulated in macrophages in advanced human atherosclerotic plaques in aorta and carotid and femoral arteries—Tampere vascular study. Ann. Med. 41:279–90 [Google Scholar]
  73. Spin JM, Hsu M, Azuma J, Tedesco MM, Deng A. 73.  et al. 2011. Transcriptional profiling and network analysis of the murine angiotensin II–induced abdominal aortic aneurysm. Physiol. Genom. 43:993–1003 [Google Scholar]
  74. Satoh H, Nakamura M, Satoh M, Nakajima T, Izumoto H. 74.  et al. 2004. Expression and localization of tumour necrosis factor-α and its converting enzyme in human abdominal aortic aneurysm. Clin. Sci. 106:301–6 [Google Scholar]
  75. Kaneko H, Anzai T, Horiuchi K, Kohno T, Nagai T. 75.  et al. 2011. Tumor necrosis factor-α converting enzyme is a key mediator of abdominal aortic aneurysm development. Atherosclerosis 218:470–78 [Google Scholar]
  76. Obama T, Tsuji T, Kobayashi T, Fukuda Y, Takayanagi T. 76.  et al. 2014. Epidermal growth factor receptor inhibitor protects abdominal aortic aneurysm in a mouse model. Clin. Sci. 128:559–65 [Google Scholar]
  77. Montiel M, de la Blanca EP, Jimenez E. 77.  2005. Angiotensin II induces focal adhesion kinase/paxillin phosphorylation and cell migration in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun. 327:971–78 [Google Scholar]
  78. Maretzky T, Evers A, Zhou W, Swendeman SL, Wong PM. 78.  et al. 2011. Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17. Nat. Commun. 2:229 [Google Scholar]
  79. Burger D, Montezano AC, Nishigaki N, He Y, Carter A, Touyz RM. 79.  2011. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/Rho kinase pathways targeted to lipid rafts. Arterioscler. Thromb. Vasc. Biol. 31:1898–907 [Google Scholar]
  80. Al-Ani B, Hewett PW, Cudmore MJ, Fujisawa T, Saifeddine M. 80.  et al. 2010. Activation of proteinase-activated receptor 2 stimulates soluble vascular endothelial growth factor receptor 1 release via epidermal growth factor receptor transactivation in endothelial cells. Hypertension 55:689–97 [Google Scholar]
  81. Chen K, Thomas SR, Albano A, Murphy MP, Keaney JF Jr. 81.  2004. Mitochondrial function is required for hydrogen peroxide-induced growth factor receptor transactivation and downstream signaling. J. Biol. Chem. 279:35079–86 [Google Scholar]
  82. Cheng J, Garcia V, Ding Y, Wu CC, Thakar K. 82.  et al. 2012. Induction of angiotensin-converting enzyme and activation of the renin-angiotensin system contribute to 20-hydroxyeicosatetraenoic acid–mediated endothelial dysfunction. Arterioscler. Thromb. Vasc. Biol. 32:1917–24 [Google Scholar]
  83. Vacaresse N, Lajoie-Mazenc I, Auge N, Suc I, Frisach MF. 83.  et al. 1999. Activation of epithelial growth factor receptor pathway by unsaturated fatty acids. Circ. Res. 85:892–99 [Google Scholar]
  84. Wang Y, Roche O, Xu C, Moriyama EH, Heir P. 84.  et al. 2012. Hypoxia promotes ligand-independent EGF receptor signaling via hypoxia-inducible factor-mediated upregulation of caveolin-1. PNAS 109:4892–97 [Google Scholar]
  85. Oliveira CJ, Schindler F, Ventura AM, Morais MS, Arai RJ. 85.  et al. 2003. Nitric oxide and cGMP activate the Ras-MAP kinase pathway-stimulating protein tyrosine phosphorylation in rabbit aortic endothelial cells. Free Radic. Biol. Med. 35:381–96 [Google Scholar]
  86. Yamamoto K, Kakino A, Takeshita H, Hayashi N, Li L. 86.  et al. 2015. Oxidized LDL (oxLDL) activates the angiotensin II type 1 receptor by binding to the lectin-like oxLDL receptor. FASEB J. 29:3342–56 [Google Scholar]
  87. Batenburg WW, Jansen PM, van den Bogaerdt AJ, AHJ Danser. 87.  2012. Angiotensin II–aldosterone interaction in human coronary microarteries involves GPR30, EGFR, and endothelial NO synthase. Cardiovasc. Res. 94:136–43 [Google Scholar]
  88. Jung O, Schreiber JG, Geiger H, Pedrazzini T, Busse R, Brandes RP. 88.  2004. gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation 109:1795–801 [Google Scholar]
  89. Helle F, Jouzel C, Chadjichristos C, Placier S, Flamant M. 89.  et al. 2009. Improvement of renal hemodynamics during hypertension-induced chronic renal disease: role of EGF receptor antagonism. Am. J. Physiol. Ren. Physiol. 297:F191–99 [Google Scholar]
  90. Griol-Charhbili V, Fassot C, Messaoudi S, Perret C, Agrapart V, Jaisser F. 90.  2011. Epidermal growth factor receptor mediates the vascular dysfunction but not the remodeling induced by aldosterone/salt. Hypertension 57:238–44 [Google Scholar]
  91. Galan M, Kassan M, Choi SK, Partyka M, Trebak M. 91.  et al. 2012. A novel role for epidermal growth factor receptor tyrosine kinase and its downstream endoplasmic reticulum stress in cardiac damage and microvascular dysfunction in type 1 diabetes mellitus. Hypertension 60:71–80 [Google Scholar]
  92. Belmadani S, Palen DI, Gonzalez-Villalobos RA, Boulares HA, Matrougui K. 92.  2008. Elevated epidermal growth factor receptor phosphorylation induces resistance artery dysfunction in diabetic db/db mice. Diabetes 57:1629–37 [Google Scholar]
  93. Hewing NJ, Weskamp G, Vermaat J, Farage E, Glomski K. 93.  et al. 2013. Intravitreal injection of TIMP3 or the EGFR inhibitor erlotinib offers protection from oxygen-induced retinopathy in mice. Invest. Ophthalmol. Vis. Sci. 54:864–70 [Google Scholar]
  94. Weskamp G, Mendelson K, Swendeman S, Le Gall S, Ma Y. 94.  et al. 2010. Pathological neovascularization is reduced by inactivation of ADAM17 in endothelial cells but not in pericytes. Circ. Res. 106:932–40 [Google Scholar]
  95. Wilson CL, Gough PJ, Chang CA, Chan CK, Frey JM. 95.  et al. 2013. Endothelial deletion of ADAM17 in mice results in defective remodeling of the semilunar valves and cardiac dysfunction in adults. Mech. Dev. 130:272–89 [Google Scholar]
  96. Thomas WG, Brandenburger Y, Autelitano DJ, Pham T, Qian H, Hannan RD. 96.  2002. Adenoviral-directed expression of the type 1A angiotensin receptor promotes cardiomyocyte hypertrophy via transactivation of the epidermal growth factor receptor. Circ. Res. 90:135–42 [Google Scholar]
  97. Smith NJ, Chan HW, Qian H, Bourne AM, Hannan KM. 97.  et al. 2011. Determination of the exact molecular requirements for type 1 angiotensin receptor epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy. Hypertension 57:973–80 [Google Scholar]
  98. Asakura M, Kitakaze M, Takashima S, Liao Y, Ishikura F. 98.  et al. 2002. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nat. Med. 8:35–40 [Google Scholar]
  99. De Giusti VC, Nolly MB, Yeves AM, Caldiz CI, Villa-Abrille MC. 99.  et al. 2011. Aldosterone stimulates the cardiac Na+/H+ exchanger via transactivation of the epidermal growth factor receptor. Hypertension 58:912–19 [Google Scholar]
  100. Wang X, Oka T, Chow FL, Cooper SB, Odenbach J. 100.  et al. 2009. Tumor necrosis factor-α–converting enzyme is a key regulator of agonist-induced cardiac hypertrophy and fibrosis. Hypertension 54:575–82 [Google Scholar]
  101. Zeng SY, Chen X, Chen SR, Li Q, Wang YH. 101.  et al. 2013. Upregulation of Nox4 promotes angiotensin II–induced epidermal growth factor receptor activation and subsequent cardiac hypertrophy by increasing ADAM17 expression. Can. J. Cardiol. 29:1310–19 [Google Scholar]
  102. Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG. 102.  et al. 2007. β-arrestin–mediated β1-adrenergic receptor transactivation of the EGFR confers cardioprotection. J. Clin. Investig. 117:2445–58 [Google Scholar]
  103. Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ. 103.  et al. 2008. β-blockers alprenolol and carvedilol stimulate β-arrestin-mediated EGFR transactivation. PNAS 105:14555–60 [Google Scholar]
  104. Rakesh K, Yoo B, Kim IM, Salazar N, Kim KS, Rockman HA. 104.  2010. β-arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci. Signal. 3:ra46 [Google Scholar]
  105. Miao Y, Bi XY, Zhao M, Jiang HK, Liu JJ. 105.  et al. 2015. Acetylcholine inhibits tumor necrosis factor α activated endoplasmic reticulum apoptotic pathway via EGFR-PI3K signaling in cardiomyocytes. J. Cell Physiol. 230:767–74 [Google Scholar]
  106. Grisanti LA, Talarico JA, Carter RL, Yu JE, Repas AA. 106.  et al. 2014. β-adrenergic receptor-mediated transactivation of epidermal growth factor receptor decreases cardiomyocyte apoptosis through differential subcellular activation of ERK1/2 and Akt. J. Mol. Cell Cardiol. 72:39–51 [Google Scholar]
  107. Talarico JA, Carter RL, Grisanti LA, Yu JE, Repas AA, Tilley DG. 107.  2014. β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo. PLOS ONE 9:e99195 [Google Scholar]
  108. Wang D, Yu X, Cohen RA, Brecher P. 108.  2000. Distinct effects of N-acetylcysteine and nitric oxide on angiotensin II–induced epidermal growth factor receptor phosphorylation and intracellular Ca2+ levels. J. Biol. Chem. 275:12223–30 [Google Scholar]
  109. Sabri A, Short J, Guo J, Steinberg SF. 109.  2002. Protease-activated receptor-1-mediated DNA synthesis in cardiac fibroblast is via epidermal growth factor receptor transactivation: distinct PAR-1 signaling pathways in cardiac fibroblasts and cardiomyocytes. Circ. Res. 91:532–39 [Google Scholar]
  110. Seta K, Sadoshima J. 110.  2003. Phosphorylation of tyrosine 319 of the angiotensin II type 1 receptor mediates angiotensin II–induced trans-activation of the epidermal growth factor receptor. J. Biol. Chem. 278:9019–26 [Google Scholar]
  111. Chen CH, Cheng TH, Lin H, Shih NL, Chen YL. 111.  et al. 2006. Reactive oxygen species generation is involved in epidermal growth factor receptor transactivation through the transient oxidization of Src homology 2–containing tyrosine phosphatase in endothelin-1 signaling pathway in rat cardiac fibroblasts. Mol. Pharmacol. 69:1347–55 [Google Scholar]
  112. Cai J, Yi FF, Yang L, Shen DF, Yang Q. 112.  et al. 2009. Targeted expression of receptor-associated late transducer inhibits maladaptive hypertrophy via blocking epidermal growth factor receptor signaling. Hypertension 53:539–48 [Google Scholar]
  113. Zhai P, Galeotti J, Liu J, Holle E, Yu X. 113.  et al. 2006. An angiotensin II type 1 receptor mutant lacking epidermal growth factor receptor transactivation does not induce angiotensin II–mediated cardiac hypertrophy. Circ. Res. 99:528–36 [Google Scholar]
  114. Messaoudi S, Zhang AD, Griol-Charhbili V, Escoubet B, Sadoshima J. 114.  et al. 2012. The epidermal growth factor receptor is involved in angiotensin II but not aldosterone/salt-induced cardiac remodelling. PLOS ONE 7:e30156 [Google Scholar]
  115. McCurley A, Pires PW, Bender SB, Aronovitz M, Zhao MJ. 115.  et al. 2012. Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors. Nat. Med. 18:1429–33 [Google Scholar]
  116. Li C, Zhang YY, Frieler RA, Zheng XJ, Zhang WC. 116.  et al. 2014. Myeloid mineralocorticoid receptor deficiency inhibits aortic constriction-induced cardiac hypertrophy in mice. PLOS ONE 9:e110950 [Google Scholar]
  117. Schreier B, Rabe S, Winter S, Ruhs S, Mildenberger S. 117.  et al. 2014. Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor. Sci. Rep. 4:7430 [Google Scholar]
  118. Eckel RH, Kahn R, Robertson RM, Rizza RA. 118.  2006. Preventing cardiovascular disease and diabetes: a call to action from the American Diabetes Association and the American Heart Association. Circulation 113:2943–46 [Google Scholar]
  119. Prada PO, Ropelle ER, Mourao RH, de Souza CT, Pauli JR. 119.  et al. 2009. EGFR tyrosine kinase inhibitor (PD153035) improves glucose tolerance and insulin action in high-fat diet-fed mice. Diabetes 58:2910–19 [Google Scholar]
  120. Grisanti LA, Repas AA, Talarico JA, Gold JI, Carter RL. 120.  et al. 2015. Temporal and gefitinib-sensitive regulation of cardiac cytokine expression via chronic β-adrenergic receptor stimulation. Am. J. Physiol. Heart Circ. Physiol. 308:H316–30 [Google Scholar]
  121. Chen B, Bronson RT, Klaman LD, Hampton TG, Wang JF. 121.  et al. 2000. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat. Genet. 24:296–99 [Google Scholar]
  122. Barrick CJ, Yu M, Chao HH, Threadgill DW. 122.  2008. Chronic pharmacologic inhibition of EGFR leads to cardiac dysfunction in C57BL/6J mice. Toxicol. Appl. Pharmacol. 228:315–25 [Google Scholar]
  123. Barrick CJ, Roberts RB, Rojas M, Rajamannan NM, Suitt CB. 123.  et al. 2009. Reduced EGFR causes abnormal valvular differentiation leading to calcific aortic stenosis and left ventricular hypertrophy in C57BL/6J but not 129S1/SvImJ mice. Am. J. Physiol. Heart Circ. Physiol. 297:H65–75 [Google Scholar]
  124. Benter IF, Juggi JS, Khan I, Yousif MH, Canatan H, Akhtar S. 124.  2005. Signal transduction mechanisms involved in cardiac preconditioning: role of Ras-GTPase, Ca2+/calmodulin-dependent protein kinase II and epidermal growth factor receptor. Mol. Cell Biochem. 268:175–83 [Google Scholar]
  125. Forster K, Kuno A, Solenkova N, Felix SB, Krieg T. 125.  2007. The δ-opioid receptor agonist DADLE at reperfusion protects the heart through activation of pro-survival kinases via EGF receptor transactivation. Am. J. Physiol. Heart Circ. Physiol. 293:H1604–8 [Google Scholar]
  126. Akhtar S, Yousif MH, Chandrasekhar B, Benter IF. 126.  2012. Activation of EGFR/ERBB2 via pathways involving ERK1/2, P38 MAPK, AKT and FOXO enhances recovery of diabetic hearts from ischemia-reperfusion injury. PLOS ONE 7:e39066 [Google Scholar]
  127. Feng M, Xiang JZ, Ming ZY, Fu Q, Ma R. 127.  et al. 2012. Activation of epidermal growth factor receptor mediates reperfusion arrhythmias in anaesthetized rats. Cardiovasc. Res. 93:60–68 [Google Scholar]
  128. Hammoud L, Lu X, Lei M, Feng Q. 128.  2011. Deficiency in TIMP-3 increases cardiac rupture and mortality post-myocardial infarction via EGFR signaling: beneficial effects of cetuximab. Basic Res. Cardiol. 106:459–71 [Google Scholar]
  129. Zhuang S, Liu N. 129.  2014. EGFR signaling in renal fibrosis. Kidney Int. Suppl. 4:70–74 [Google Scholar]
  130. Uchiyama-Tanaka Y, Matsubara H, Nozawa Y, Murasawa S, Mori Y. 130.  et al. 2001. Angiotensin II signaling and HB-EGF shedding via metalloproteinase in glomerular mesangial cells. Kidney Int. 60:2153–63 [Google Scholar]
  131. Uchiyama-Tanaka Y, Matsubara H, Mori Y, Kosaki A, Kishimoto N. 131.  et al. 2002. Involvement of HB-EGF and EGF receptor transactivation in TGF-β-mediated fibronectin expression in mesangial cells. Kidney Int. 62:799–808 [Google Scholar]
  132. Uttarwar L, Peng F, Wu D, Kumar S, Gao B. 132.  et al. 2011. HB-EGF release mediates glucose-induced activation of the epidermal growth factor receptor in mesangial cells. Am. J. Physiol. Ren. Physiol. 300:F921–31 [Google Scholar]
  133. Taniguchi K, Xia L, Goldberg HJ, Lee KW, Shah A. 133.  et al. 2013. Inhibition of Src kinase blocks high glucose-induced EGFR transactivation and collagen synthesis in mesangial cells and prevents diabetic nephropathy in mice. Diabetes 62:3874–86 [Google Scholar]
  134. Huang S, Zhang A, Ding G, Chen R. 134.  2009. Aldosterone-induced mesangial cell proliferation is mediated by EGF receptor transactivation. Am. J. Physiol. Ren. Physiol. 296:F1323–33 [Google Scholar]
  135. Dey M, Baldys A, Sumter DB, Gooz P, Luttrell LM. 135.  et al. 2010. Bradykinin decreases podocyte permeability through ADAM17-dependent epidermal growth factor receptor activation and zonula occludens-1 rearrangement. J. Pharmacol. Exp. Ther. 334:775–83 [Google Scholar]
  136. Chen J, Chen JK, Neilson EG, Harris RC. 136.  2006. Role of EGF receptor activation in angiotensin II–induced renal epithelial cell hypertrophy. J. Am. Soc. Nephrol. 17:1615–23 [Google Scholar]
  137. Chen J, Chen JK, Harris RC. 137.  2012. Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway. Mol. Cell. Biol. 32:981–91 [Google Scholar]
  138. Zhuang S, Yan Y, Han J, Schnellmann RG. 138.  2005. p38 kinase–mediated transactivation of the epidermal growth factor receptor is required for dedifferentiation of renal epithelial cells after oxidant injury. J. Biol. Chem. 280:21036–42 [Google Scholar]
  139. Rayego-Mateos S, Morgado-Pascual JL, Sanz AB, Ramos AM, Eguchi S. 139.  et al. 2013. TWEAK transactivation of the epidermal growth factor receptor mediates renal inflammation. J. Pathol. 231:480–94 [Google Scholar]
  140. Lee YJ, Han HJ. 140.  2008. Albumin-stimulated DNA synthesis is mediated by Ca2+/PKC as well as EGF receptor–dependent p44/42 MAPK and NF-κB signal pathways in renal proximal tubule cells. Am. J. Physiol. Ren. Physiol. 294:F534–41 [Google Scholar]
  141. Reich H, Tritchler D, Herzenberg AM, Kassiri Z, Zhou X. 141.  et al. 2005. Albumin activates ERK via EGF receptor in human renal epithelial cells. J. Am. Soc. Nephrol. 16:1266–78 [Google Scholar]
  142. Singh AB, Sugimoto K, Harris RC. 142.  2007. Juxtacrine activation of epidermal growth factor (EGF) receptor by membrane-anchored heparin-binding EGF-like growth factor protects epithelial cells from anoikis while maintaining an epithelial phenotype. J. Biol. Chem. 282:32890–901 [Google Scholar]
  143. Arar M, Zajicek HK, Elshihabi I, Levi M. 143.  1999. Epidermal growth factor inhibits Na-Pi cotransport in weaned and suckling rats. Am. J. Physiol. 276:F72–78 [Google Scholar]
  144. Groenestege WM, Thebault S, van der Wijst J, van den Berg D, Janssen R. 144.  et al. 2007. Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J. Clin. Investig. 117:2260–67 [Google Scholar]
  145. Grossmann C, Freudinger R, Mildenberger S, Krug AW, Gekle M. 145.  2004. Evidence for epidermal growth factor receptor as negative-feedback control in aldosterone-induced Na+ reabsorption. Am. J. Physiol. Ren. Physiol. 286:F1226–31 [Google Scholar]
  146. McEneaney V, Harvey BJ, Thomas W. 146.  2007. Aldosterone rapidly activates protein kinase D via a mineralocorticoid receptor/EGFR trans-activation pathway in the M1 kidney CCD cell line. J. Steroid Biochem. Mol. Biol. 107:180–90 [Google Scholar]
  147. Capdevila J, Wang W. 147.  2013. Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension. Curr. Opin. Nephrol. Hypertens. 22:163–69 [Google Scholar]
  148. Chen JK, Capdevila J, Harris RC. 148.  2002. Heparin-binding EGF-like growth factor mediates the biological effects of P450 arachidonate epoxygenase metabolites in epithelial cells. PNAS 99:6029–34 [Google Scholar]
  149. Zhao H, Tian W, Tai C, Cohen DM. 149.  2003. Hypertonic induction of COX-2 expression in renal medullary epithelial cells requires transactivation of the EGFR. Am. J. Physiol. Ren. Physiol. 285:F281–88 [Google Scholar]
  150. Wang Z, Chen JK, Wang SW, Moeckel G, Harris RC. 150.  2003. Importance of functional EGF receptors in recovery from acute nephrotoxic injury. J. Am. Soc. Nephrol. 14:3147–54 [Google Scholar]
  151. Chen J, Chen JK, Harris RC. 151.  2012. Deletion of the epidermal growth factor receptor in renal proximal tubule epithelial cells delays recovery from acute kidney injury. Kidney Int. 82:45–52 [Google Scholar]
  152. Tang J, Liu N, Tolbert E, Ponnusamy M, Ma L. 152.  et al. 2013. Sustained activation of EGFR triggers renal fibrogenesis after acute kidney injury. Am. J. Pathol. 183:160–72 [Google Scholar]
  153. Bollee G, Flamant M, Schordan S, Fligny C, Rumpel E. 153.  et al. 2011. Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis. Nat. Med. 17:1242–50 [Google Scholar]
  154. Francois H, Placier S, Flamant M, Tharaux PL, Chansel D. 154.  et al. 2004. Prevention of renal vascular and glomerular fibrosis by epidermal growth factor receptor inhibition. FASEB J. 18:926–28 [Google Scholar]
  155. Lautrette A, Li S, Alili R, Sunnarborg SW, Burtin M. 155.  et al. 2005. Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach. Nat. Med. 11:867–74 [Google Scholar]
  156. Che Q, Carmines PK. 156.  2002. Angiotensin II triggers EGFR tyrosine kinase-dependent Ca2+ influx in afferent arterioles. Hypertension 40:700–6 [Google Scholar]
  157. Wassef L, Kelly DJ, Gilbert RE. 157.  2004. Epidermal growth factor receptor inhibition attenuates early kidney enlargement in experimental diabetes. Kidney Int. 66:1805–14 [Google Scholar]
  158. Zhang MZ, Wang Y, Paueksakon P, Harris RC. 158.  2014. Epidermal growth factor receptor inhibition slows progression of diabetic nephropathy in association with a decrease in endoplasmic reticulum stress and an increase in autophagy. Diabetes 63:2063–72 [Google Scholar]
  159. Chen J, Chen JK, Harris RC. 159.  2015. EGF receptor deletion in podocytes attenuates diabetic nephropathy. J. Am. Soc. Nephrol. 26:1115–25 [Google Scholar]
  160. Terzi F, Burtin M, Hekmati M, Federici P, Grimber G. 160.  et al. 2000. Targeted expression of a dominant-negative EGF-R in the kidney reduces tubulo-interstitial lesions after renal injury. J. Clin. Investig. 106:225–34 [Google Scholar]
  161. Liu N, Guo JK, Pang M, Tolbert E, Ponnusamy M. 161.  et al. 2012. Genetic or pharmacologic blockade of EGFR inhibits renal fibrosis. J. Am. Soc. Nephrol. 23:854–67 [Google Scholar]
  162. Sweeney WE, Chen Y, Nakanishi K, Frost P, Avner ED. 162.  2000. Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor. Kidney Int. 57:33–40 [Google Scholar]
  163. Chen MH, Kerkela R, Force T. 163.  2008. Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation 118:84–95 [Google Scholar]
  164. Grimminger F, Schermuly RT, Ghofrani HA. 164.  2010. Targeting non-malignant disorders with tyrosine kinase inhibitors. Nat. Rev. Drug Discov. 9:956–70 [Google Scholar]
  165. Tejpar S, Piessevaux H, Claes K, Piront P, Hoenderop JG. 165.  et al. 2007. Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol. 8:387–94 [Google Scholar]
  166. Izzedine H, Rixe O, Billemont B, Baumelou A, Deray G. 166.  2007. Angiogenesis inhibitor therapies: focus on kidney toxicity and hypertension. Am. J. Kidney Dis. 50:203–18 [Google Scholar]
  167. Morange PE, Tregouet DA, Godefroy T, Saut N, Bickel C. 167.  et al. 2008. Polymorphisms of the tumor necrosis factor-alpha (TNF) and the TNF-alpha converting enzyme (TACE/ADAM17) genes in relation to cardiovascular mortality: the AtheroGene study. J. Mol. Med. 86:1153–61 [Google Scholar]
  168. Moss ML, Sklair-Tavron L, Nudelman R. 168.  2008. Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis. Nat. Clin. Pract. Rheumatol. 4:300–9 [Google Scholar]
  169. Kwok HF, Botkjaer KA, Tape CJ, Huang Y, McCafferty J, Murphy G. 169.  2014. Development of a ‘mouse and human cross-reactive’ affinity-matured exosite inhibitory human antibody specific to TACE (ADAM17) for cancer immunotherapy. Protein Eng. Des. Sel. 27:179–90 [Google Scholar]
  170. Lambert DW, Yarski M, Warner FJ, Thornhill P, Parkin ET. 170.  et al. 2005. Tumor necrosis factor-α convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2). J. Biol. Chem. 280:30113–19 [Google Scholar]
  171. Santos RA. 171.  2014. Angiotensin-(1–7). Hypertension 63:1138–47 [Google Scholar]
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