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Abstract: SA-PO627

Differential Roles of RAGE Species for Renal Tubular Damages

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation


  • Miyagawa, Taro, Kanazawa University, Kanazawa, Japan
  • Iwata, Yasunori, Kanazawa University, Kanazawa, Japan
  • Ogura, Hisayuki, Kanazawa University, Kanazawa, Japan
  • Sato, Koichi, Kanazawa University, Kanazawa, Japan
  • Kitajima, Shinji, Kanazawa University, Kanazawa, Japan
  • Toyama, Tadashi, Kanazawa University, Kanazawa, Japan
  • Hara, Akinori, Kanazawa University, Kanazawa, Japan
  • Sakai, Norihiko, Kanazawa University, Kanazawa, Japan
  • Shimizu, Miho, Kanazawa University, Kanazawa, Japan
  • Furuichi, Kengo, Kanazawa Medical University, Kahoku-Gun, Japan
  • Yamamoto, Yasuhiko, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
  • Wada, Takashi, Kanazawa University, Kanazawa, Japan

Receptor for advanced glycation end-products (receptor for AGEs, RAGE) is a transmembrane and multiligand pattern recognition receptor, which binds AGEs, S100 proteins, and high mobility group box 1 protein (HMGB1), eliciting inflammatory signal transductions. Soluble and decoy forms of RAGE (sRAGE) are, otherwise, generated by a cleavage of RAGE or by an alternative splicing, which forms an endogenous secretary RAGE (esRAGE). However, roles of sRAGE in the pathogenesis of kidney diseases remains unclear. We here examined whether RAGE and sRAGE could be implicated in renal tubular damages using a mouse kidney ischemia/reperfusion (I/R) model.


Unilateral renal I/R was introduced in RAGE knockout (Ager-/-) mice with or without administration of sRAGE. Tubular damages, interstitial cell accumulation and fibrosis were assessed at day 2 or 7. We also assessed tubular damages using anti-glomerular basement membrane nephritis models with or without sRAGE treatment at day 7. We checked the expression of genes coding RAGE, esRAGE and proinflammatory mediators after hypoxia using murine renal proximal tubular epithelial (mProx24) cells. Cellular damages and proliferation were also assessed in hypoxia-induced mProx24 cells with or without an sRAGE addition.


We found that tubular damages were severer in Ager-/- mice than in Ager+/+ mice at day 2 and 7 after I/R. Kidney fibrosis and macrophage infiltration were also exaggerated in Ager-/- mice at day7. In vitro, hypoxia-exposure decreased the expression of genes coding RAGE and esRAGE in mProx24 cells, while Hmgb1 and Tnfa mRNAs were paradoxically upregulated. However, an sRAGE addition significantly decreased Hmgb1 and Tnfa mRNA expressions and induced the proliferation in hypoxia-induced mProx24 cells. Moreover, an sRAGE administration protected from tubular damages of I/R-performed mice and of the anti-GBM glomerulonephritis models.


We demonstrated that the hypoxic condition could induce the downregulation of genes coding RAGE and esRAGE in renal tubular cells. Administration of sRAGE could protect the kidney from I/R injury.