Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy

Tomoki Kosugi, Yukio Yuzawa, Waichi Sato, Hanayo Arata-Kawai, Norihiko Suzuki, Noritoshi Kato, Seiichi Matsuo, Kenji Kadomatsu

研究成果: Article査読

66 被引用数 (Scopus)

抄録

The concept that inflammation plays a crucial role in the pathogenesis of diabetic nephropathy has been recently emerging, although the principal pathology of diabetic nephropathy comprises glomerular sclerosis and associated changes in nephrons. Here, we identified the growth factor midkine (MK) as a novel key molecule involved in inflammation associated with Streptozotocin- induced diabetic nephropathy. The tubulointerstitial damage, as assessed as morphological changes, osteopontin expression, collagen I deposition and macrophage infiltration, were strikingly less in MK-deficient (Mdk -/-) mice than in Mdk+/+ mice. Monocyte chemoattractant protein (MCP)-1 expression, but not that of intercellular adhesion molecule-1, was also lower in Mdk-/- mice. High glucose upregulated MK expression in primary-cultured tubular epithelial cells, and induced MCP-1 to a larger extent in Mdk+/+ cells than in Mdk-/- cells. Correspondingly, the combination of exogenous MK and high glucose enhanced MCP-1 expression in Mdk-/- cells. Furthermore, high glucose and oxidant stress enhanced MK expression in macrophages. Consistent with the findings in the mouse model, MK expression was detected in the glomeruli, tubular epithelium and interstitium of kidneys from patients with diabetic nephropathy. Our data indicate that MK plays a critical role in the tubulointerstitial inflammation associated with diabetic nephropathy through activation of the MCP-1 pathway.

本文言語English
ページ(範囲)903-913
ページ数11
ジャーナルLaboratory Investigation
87
9
DOI
出版ステータスPublished - 09-2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • 病理学および法医学
  • 分子生物学
  • 細胞生物学

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