Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes

Shinichi Okada, Kenichi Shikata, Mitsuhiro Matsuda, Daisuke Ogawa, Hitomi Usui, Yuichi Kido, Ryo Nagase, Jun Wada, Yasushi Shikata, Hirofumi Makino

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression of transforming growth factor (TGF)-β, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of ICAM-1 in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1-/-) mice and ICAM-I+/+ mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1-/- mice compared with that of ICAM-1+/+ mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1-/- mice than in diabetic ICAM-1+/+ mice. Moreover, expressions of TGF-β and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1-/- mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.

Original languageEnglish
Pages (from-to)2586-2593
Number of pages8
JournalDiabetes
Volume52
Issue number10
DOIs
Publication statusPublished - Oct 1 2003

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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