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Annual Review of Medicine

Volume 69, 2018

Targeting RAGE Signaling in Inflammatory Disease

Abstract

The receptor for advanced glycation end-products (RAGE) is a multiligand pattern recognition receptor implicated in diverse chronic inflammatory states. RAGE binds and mediates the cellular response to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA. RAGE can also act as an innate immune sensor of microbial pathogen-associated molecular pattern molecules (PAMPs) including bacterial endotoxin, respiratory viruses, and microbial DNA. RAGE is expressed at low levels under normal physiology, but it is highly upregulated under chronic inflammation because of the accumulation of various RAGE ligands. Blocking RAGE signaling in cell and animal models has revealed that targeting RAGE impairs inflammation and progression of diabetic vascular complications, cardiovascular disease (CVD), and cancer progression and metastasis. The clinical relevance of RAGE in inflammatory disease is being demonstrated in emerging clinical trials of novel small-molecule RAGE inhibitors.

Keyword(s): cancer, cardiovascular disease, diabetes, HMGB1, inflammation, pattern recognition receptors, receptor for advanced glycation end-products, S100 proteins, small-molecule inhibitors
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2018-01-29
2024-04-23
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Literature Cited

  1. Neeper M, Schmidt AM, Brett J. 1.  et al. 1992. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J. Biol. Chem. 267:14998–5004 [Google Scholar]
  2. Chavakis T, Bierhaus A, Al-Fakhri N. 2.  et al. 2003. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J. Exp. Med. 198:1507–15This paper defined RAGE as a PRR. [Google Scholar]
  3. Kalea AZ, Schmidt AM, Hudson BI. 3.  2009. RAGE: a novel biological and genetic marker for vascular disease. Clin. Sci. 116:621–37 [Google Scholar]
  4. Kierdorf K, Fritz G. 4.  2013. RAGE regulation and signaling in inflammation and beyond. J. Leukoc. Biol. 94:55–68 [Google Scholar]
  5. Constien R, Forde A, Liliensiek B. 5.  et al. 2001. Characterization of a novel EGFP reporter mouse to monitor Cre recombination as demonstrated by a Tie2 Cre mouse line. Genesis 30:36–44 [Google Scholar]
  6. Burstein AH, Grimes I, Galasko DR. 6.  et al. 2014. Effect of TTP488 in patients with mild to moderate Alzheimer's disease. BMC Neurol 14:12 [Google Scholar]
  7. Deane R, Singh I, Sagare AP. 7.  et al. 2012. A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J. Clin. Investig. 122:1377–92 [Google Scholar]
  8. Brownlee M. 8.  1995. Advanced protein glycosylation in diabetes and aging. Annu. Rev. Med. 46:223–34 [Google Scholar]
  9. Trivelli L, Ranney HM, Lai HTL. 9.  1971. Hemoglobin components in patients with diabetes mellitus. N. Engl. J. Med. 284:353–57 [Google Scholar]
  10. 10. The Diabetes Control and Complications Trial Research Group. 1993. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 329:977–86The DCCT was a landmark study that clearly linked control of glucose and glycation to diabetic vascular complications. [Google Scholar]
  11. Stratton IM, Adler AI, Neil HA. 11.  et al. 2001. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–12 [Google Scholar]
  12. Thornalley PJ, Langborg A, Minhas HS. 12.  1999. Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem. J. 344:109–16 [Google Scholar]
  13. Kislinger T, Fu C, Huber C. 13.  et al. 1999. N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J. Biol. Chem. 274:31740–49 [Google Scholar]
  14. Fritz G. 14.  2011. RAGE: a single receptor fits multiple ligands. Trends Biochem. Sci. 36:625–32 [Google Scholar]
  15. Hudson BI, Kalea AZ, Arriero MD. 15.  et al. 2008. Interaction of the RAGE cytoplasmic domain with diaphanous-1 is required for ligand-stimulated cellular migration through activation of Rac1 and Cdc42. J. Biol. Chem. 283:34457–68 [Google Scholar]
  16. Sessa L, Gatti E, Zeni F. 16.  et al. 2014. The receptor for advanced glycation end-products (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs). PLOS ONE 9:e86903 [Google Scholar]
  17. Cavallaro U, Dejana E. 17.  2011. Adhesion molecule signalling: not always a sticky business. Nat. Rev. Mol. Cell Biol. 12:189–97 [Google Scholar]
  18. Sugaya K, Fukagawa T, Matsumoto KI. 18.  et al. 1994. Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3. Genomics 23:408–19 [Google Scholar]
  19. Hudson BI, Carter AM, Harja E. 19.  et al. 2008. Identification, classification, and expression of RAGE gene splice variants. FASEB J 22:1572–80 [Google Scholar]
  20. Kalea AZ, Reiniger N, Yang H. 20.  et al. 2009. Alternative splicing of the murine receptor for advanced glycation end-products (RAGE) gene. FASEB J 23:1766–74 [Google Scholar]
  21. Fehrenbach H, Kasper M, Tschernig T. 21.  et al. 1998. Receptor for advanced glycation endproducts (RAGE) exhibits highly differential cellular and subcellular localisation in rat and human lung. Cell Mol. Biol. 44:1147–57 [Google Scholar]
  22. Hori O, Brett J, Slattery T. 22.  et al. 1995. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of RAGE and amphoterin in the developing nervous system. J. Biol. Chem. 270:25752–61Demonstrated that RAGE can bind other ligands than AGEs. [Google Scholar]
  23. Yan SD, Chen X, Fu J. 23.  et al. 1996. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 382:685–91 [Google Scholar]
  24. Hofmann MA, Drury S, Fu CF. 24.  et al. 1999. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97:889–901 [Google Scholar]
  25. Suresh R, Mosser DM. 25.  2013. Pattern recognition receptors in innate immunity, host defense, and immunopathology. Adv. Physiol. Educ. 37:284–91 [Google Scholar]
  26. Scaffidi P, Misteli T, Bianchi ME. 26.  2002. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–95 [Google Scholar]
  27. Kang R, Zhang Q, Zeh HJ III. 27.  et al. 2013. HMGB1 in cancer: good, bad, or both?. Clin. Cancer Res. 19:4046–57 [Google Scholar]
  28. Wang H, Bloom O, Zhang M. 28.  et al. 1999. HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–51 [Google Scholar]
  29. Donato R. 29.  2001. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int. J. Biochem. Cell Biol. 33:637–68 [Google Scholar]
  30. Leclerc E, Fritz G, Vetter SW, Heizmann CW. 30.  2009. Binding of S100 proteins to RAGE: an update. Biochim. Biophys. Acta 1793:993–1007 [Google Scholar]
  31. Ostendorp T, Leclerc E, Galichet A. 31.  et al. 2007. Structural and functional insights into RAGE activation by multimeric S100B. EMBO J 26:3868–78 [Google Scholar]
  32. Perera C, McNeil HP, Geczy CL. 32.  2010. S100 Calgranulins in inflammatory arthritis. Immunol. Cell Biol. 88:41–49 [Google Scholar]
  33. Rammes A, Roth J, Goebeler M. 33.  et al. 1997. Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway. J. Biol. Chem. 272:9496–502 [Google Scholar]
  34. Bjarnason I. 34.  2017. The use of fecal calprotectin in inflammatory bowel disease. Gastroenterol. Hepatol. 13:53–56 [Google Scholar]
  35. Deane R, Du YS, Submamaryan RK. 35.  et al. 2003. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat. Med. 9:907–13 [Google Scholar]
  36. Sirois CM, Jin T, Miller AL. 36.  et al. 2013. RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA. J. Exp. Med. 210:2447–63 [Google Scholar]
  37. Liu L, Yang M, Kang R. 37.  et al. 2014. HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE. Biochem. Biophys. Res. Commun. 450:851–56 [Google Scholar]
  38. Yamamoto Y, Harashima A, Saito H. 38.  et al. 2011. Septic shock is associated with receptor for advanced glycation end products ligation of LPS. J. Immunol. 186:3248–57 [Google Scholar]
  39. Tian J, Huang K, Krishnan S. 39.  et al. 2013. RAGE inhibits human respiratory syncytial virus syncytium formation by interfering with F-protein function. J. Gen. Virol. 94:1691–700 [Google Scholar]
  40. Anisuzzaman, Hatta T, Miyoshi T. 40.  et al. 2014. Longistatin in tick saliva blocks advanced glycation end-product receptor activation. J. Clin. Investig. 124:4429–44 [Google Scholar]
  41. Uribarri J, del Castillo MD, de la Maza MP. 41.  et al. 2015. Dietary advanced glycation end products and their role in health and disease. Adv. Nutr. 6:461–73 [Google Scholar]
  42. Stirban A, Negrean M, Gotting C. 42.  et al. 2008. Dietary advanced glycation endproducts and oxidative stress: in vivo effects on endothelial function and adipokines. Ann. N. Y. Acad. Sci. 1126:276–79 [Google Scholar]
  43. Poulsen MW, Andersen JM, Hedegaard RV. 43.  et al. 2016. Short-term effects of dietary advanced glycation end products in rats. Br. J. Nutr. 115:629–36 [Google Scholar]
  44. Koch M, Chitayat S, Dattilo BM. 44.  et al. 2010. Structural basis for ligand recognition and activation of RAGE. Structure 18:1342–52 [Google Scholar]
  45. Leclerc E, Fritz G, Weibel M. 45.  et al. 2007. S100B and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycation end products) immunoglobulin domains. J. Biol. Chem. 282:31317–31 [Google Scholar]
  46. Yatime L, Betzer C, Jensen RK. 46.  et al. 2016. The structure of the RAGE:S100A6 complex reveals a unique mode of homodimerization for S100 proteins. Structure 24:2043–52 [Google Scholar]
  47. Zong H, Madden A, Ward M. 47.  et al. 2010. Homodimerization is essential for the receptor for advanced glycation end products (RAGE)-mediated signal transduction. J. Biol. Chem. 285:23137–46 [Google Scholar]
  48. Yatime L, Andersen GR. 48.  2013. Structural insights into the oligomerization mode of the human receptor for advanced glycation end-products. FEBS J 280:6556–68 [Google Scholar]
  49. Rouhiainen A, Kuja-Panula J, Tumova S, Rauvala H. 49.  2013. RAGE-mediated cell signaling. Methods Mol. Biol. 963:239–63 [Google Scholar]
  50. Sakaguchi T, Yan SF, Yan SD. 50.  et al. 2003. Central role of RAGE-dependent neointimal expansion in arterial restenosis. J. Clin. Investig. 111:959–72 [Google Scholar]
  51. Taguchi A, Blood DC, del Toro G. 51.  et al. 2000. Blockage of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405:354–60 [Google Scholar]
  52. Jules J, Miguel D, Hudson BI. 52.  2013. Alternative splicing of the RAGE cytoplasmic domain regulates cell signaling and function. PLOS ONE 8:e78267 [Google Scholar]
  53. Ishihara K, Tsutsumi K, Kawane S. 53.  et al. 2003. The receptor for advanced glycation end-products (RAGE) directly binds to ERK by a D-domain-like docking site. FEBS Lett 550:107–13 [Google Scholar]
  54. Sakaguchi M, Murata H, Yamamoto K. 54.  et al. 2011. TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PLOS ONE 6:e23132 [Google Scholar]
  55. Yamamoto K, Murata H, Putranto EW. 55.  et al. 2013. DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells. Oncol. Rep. 29:1073–79 [Google Scholar]
  56. Rai V, Maldonado AY, Burz DS. 56.  et al. 2012. Signal transduction in receptor for advanced glycation end products (RAGE): solution structure of C-terminal RAGE (ctRAGE) and its binding to mDia1. J. Biol. Chem. 287:5133–44 [Google Scholar]
  57. Wautier JL, Zoukourian C, Chappey O. 57.  et al. 1996. Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats. J. Clin. Investig. 97:238–43 [Google Scholar]
  58. Park L, Raman KG, Lee KJ. 58.  et al. 1997. A murine model of accelerated diabetic atherosclerosis: suppression by soluble receptor for advanced glycation endproducts. Circulation 96:3079 [Google Scholar]
  59. Wendt T, Harja E, Bucciarelli L. 59.  et al. 2006. RAGE modulates vascular inflammation and atherosclerosis in a murine model of type 2 diabetes. Atherosclerosis 185:70–77 [Google Scholar]
  60. Soro-Paavonen A, Watson AM, Li J. 60.  et al. 2008. Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in diabetes. Diabetes 57:2461–69 [Google Scholar]
  61. Harja E, Bu DX, Hudson BI. 61.  et al. 2008. Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE–/– mice. J. Clin. Investig. 118:183–94 [Google Scholar]
  62. Bucciarelli LG, Kaneko M, Ananthakrishnan R. 62.  et al. 2006. Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury. Circulation 113:1226–34 [Google Scholar]
  63. Tanji N, Markowitz GS, Fu CF. 63.  et al. 2000. Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease. J. Am. Soc. Nephrol. 11:1656–66 [Google Scholar]
  64. Wendt TM, Tanji N, Guo J. 64.  et al. 2003. RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am. J. Pathol. 162:1123–37 [Google Scholar]
  65. Barile GR, Pachydaki SI, Tari SR. 65.  et al. 2005. The RAGE axis in early diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 46:2916–24 [Google Scholar]
  66. Toth C, Rong LL, Yang C. 66.  et al. 2008. Receptor for advanced glycation end products (RAGEs) and experimental diabetic neuropathy. Diabetes 57:1002–17 [Google Scholar]
  67. Goova MT, Li J, Kislinger T. 67.  et al. 2001. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am. J. Pathol. 159:513–25 [Google Scholar]
  68. Juranek J, Ray R, Banach M, Rai V. 68.  2015. Receptor for advanced glycation end-products in neurodegenerative diseases. Rev. Neurosci. 26:691–98 [Google Scholar]
  69. Kang R, Tang D, Schapiro NE. 69.  et al. 2010. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death. Differ. 17:666–76 [Google Scholar]
  70. Logsdon CD, Fuentes MK, Huang EH, Arumugam T. 70.  2007. RAGE and RAGE ligands in cancer. Curr. Mol. Med. 7:777–89 [Google Scholar]
  71. Kwak T, Drews-Elger K, Ergonul A. 71.  et al. 2017. Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis. Oncogene 36:1559–72 [Google Scholar]
  72. Kalea AZ, See F, Harja E. 72.  et al. 2010. Alternatively spliced RAGEv1 inhibits tumorigenesis through suppression of JNK signaling. Cancer Res 70:5628–38 [Google Scholar]
  73. Hsieh HL, Schafer BW, Sasaki N, Heizmann CW. 73.  2003. Expression analysis of S100 proteins and RAGE in human tumors using tissue microarrays. Biochem. Biophys. Res. Commun. 307:375–81 [Google Scholar]
  74. Ishiguro H, Nakaigawa N, Miyoshi Y. 74.  et al. 2005. Receptor for advanced glycation end products (RAGE) and its ligand, amphoterin are overexpressed and associated with prostate cancer development. Prostate 64:92–100 [Google Scholar]
  75. Kuniyasu H, Chihara Y, Takahashi T. 75.  2003. Co-expression of receptor for advanced glycation end products and the ligand amphoterin associates closely with metastasis of colorectal cancer. Oncol. Rep. 10:445–48 [Google Scholar]
  76. Kuniyasu H, Oue N, Wakikawa A. 76.  et al. 2002. Expression of receptors for advanced glycation end-products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer. J. Pathol. 196:163–70 [Google Scholar]
  77. Turovskaya O, Foell D, Sinha P. 77.  et al. 2008. RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Carcinogenesis 29:2035–43 [Google Scholar]
  78. Vernon PJ, Loux TJ, Schapiro NE. 78.  et al. 2013. The receptor for advanced glycation end products promotes pancreatic carcinogenesis and accumulation of myeloid-derived suppressor cells. J. Immunol. 190:1372–79 [Google Scholar]
  79. Gebhardt C, Riehl A, Durchdewald M. 79.  et al. 2008. RAGE signaling sustains inflammation and promotes tumor development. J. Exp. Med. 205:275–85 [Google Scholar]
  80. Boyapati RK, Rossi AG, Satsangi J, Ho GT. 80.  2016. Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications. Mucosal. Immunol. 9:567–82 [Google Scholar]
  81. Hofmann MA, Drury S, Hudson BI. 81.  et al. 2003. RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response. Genes Immun 3:123–35 [Google Scholar]
  82. Hancock DB, Eijgelsheim M, Wilk JB. 82.  et al. 2010. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat. Genet. 42:45–52 [Google Scholar]
  83. Repapi E, Sayers I, Wain LV. 83.  et al. 2010. Genome-wide association study identifies five loci associated with lung function. Nat. Genet. 42:36–44 [Google Scholar]
  84. Al-Robaiy S, Weber B, Simm A. 84.  et al. 2013. The receptor for advanced glycation end-products supports lung tissue biomechanics. Am. J. Physiol. Lung Cell Mol. Physiol. 305:L491–L500 [Google Scholar]
  85. Yonekura H, Yamamoto Y, Sakurai S. 85.  et al. 2003. Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem. J. 370:1097–109 [Google Scholar]
  86. Zhang L, Bukulin M, Kojro E. 86.  et al. 2008. Receptor for advanced glycation end products is subjected to protein ectodomain shedding by metalloproteinases. J. Biol. Chem. 283:35507–16 [Google Scholar]
  87. Falcone C, Emanuele E, D'Angelo A. 87.  et al. 2005. Plasma levels of soluble receptor for advanced glycation end products and coronary artery disease in nondiabetic men. Arterioscler. Thromb. Vasc. Biol. 25:1032–37The use of serum sRAGE levels as a biomarker for clinical disease was a critical step in the understanding of RAGE in human disease. [Google Scholar]
  88. Sabbagh MN, Agro A, Bell J. 88.  et al. 2011. PF-04494700, an oral inhibitor of receptor for advanced glycation end products (RAGE), in Alzheimer disease. Alzheimer Dis. Assoc. Disord. 25:206–12 [Google Scholar]
  89. Galasko D, Bell J, Mancuso JY. 89.  et al. 2014. Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease. Neurology 82:1536–42 [Google Scholar]
  90. Kostura MA, Kindy M, Burstein AH. 90.  et al. 2014. Efficacy of RAGE antagonists in murine models of Alzheimer's disease. Alzheimer's Dement 10:4P638 [Google Scholar]
  91. Lee YS, Kim H, Kim YH. 91.  et al. 2012. Synthesis and structure-activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer's disease. Bioorg. Med. Chem. Lett. 22:7555–61 [Google Scholar]
  92. Han YT, Choi GI, Son D. 92.  et al. 2012. Ligand-based design, synthesis, and biological evaluation of 2-aminopyrimidines, a novel series of receptor for advanced glycation end products (RAGE) inhibitors. J. Med. Chem. 55:9120–35 [Google Scholar]
  93. Shen C, Ma Y, Zeng Z. 93.  et al. 2017. RAGE-specific inhibitor FPS-ZM1 attenuates AGEs-induced neuroinflammation and oxidative stress in rat primary microglia. Neurochem. Res. 42:102902–11 [Google Scholar]
  94. Li D, Lei C, Zhang S. 94.  et al. 2015. Blockade of high mobility group box-1 signaling via the receptor for advanced glycation end-products ameliorates inflammatory damage after acute intracerebral hemorrhage. Neurosci. Lett. 609:109–19 [Google Scholar]
  95. Yang F, Wang Z, Zhang JH. 95.  et al. 2015. Receptor for advanced glycation end-product antagonist reduces blood-brain barrier damage after intracerebral hemorrhage. Stroke 46:1328–36 [Google Scholar]
  96. Hong Y, Shen C, Yin Q. 96.  et al. 2016. Effects of RAGE-specific inhibitor FPS-ZM1 on amyloid-β metabolism and AGEs-induced inflammation and oxidative stress in rat hippocampus. Neurochem. Res. 41:1192–99 [Google Scholar]
  97. Liu Y, Yu M, Zhang Z. 97.  et al. 2016. Blockade of receptor for advanced glycation end products protects against systolic overload-induced heart failure after transverse aortic constriction in mice. Eur. J. Pharmacol. 791:535–43 [Google Scholar]
  98. Yao L, Zhao H, Tang H. 98.  et al. 2016. The receptor for advanced glycation end products is required for beta-catenin stabilization in a chemical-induced asthma model. Br. J. Pharmacol. 173:2600–13 [Google Scholar]
  99. Manigrasso MB, Pan J, Rai V. 99.  et al. 2016. Small molecule inhibition of ligand-stimulated RAGE-DIAPH1 signal transduction. Sci. Rep. 6:22450 [Google Scholar]
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Targeting RAGE Signaling in Inflammatory Disease
Annual Review of Medicine 69, 349 (2018); https://doi.org/10.1146/annurev-med-041316-085215
/content/journals/10.1146/annurev-med-041316-085215
/content/journals/10.1146/annurev-med-041316-085215
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