The role of megsin, a serine protease inhibitor, in diabetic mesangial matrix accumulation

Shuichi Ohtomo, Masaomi Nangaku, Yuko Izuhara, Norio Yamada, Takashi Dan, Takefumi Mori, Sadayoshi Ito, Charles Van Ypersele De Strihou, Toshio Miyata

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

In diabetic nephropathy decreased activities of matrix metalloproteinase (MMP)-2, MMP-9 and plasmin contribute to mesangial matrix accumulation. Megsin, a novel member of the serine protease inhibitor superfamily, is predominantly expressed in mesangial cells and is up-regulated in diabetic nephropathy and its overexpression spontaneously induces progressive mesangial expansion in mice. High-glucose stimulated megsin mRNA expression in an in vivo model of type II diabetic nephropathy as well as in vitro in cultured mesangial cells. Megsin potentially inhibits total enzymatic activities of MMP-2 and -9 and plasmin, indicating decreased degradation of mesangial matrix. A specific monoclonal anti-megsin neutralizing antibody restored MMP activity in a transforming growth factor-β independent manner. Our study suggests that the mesangial matrix accumulation caused by hyperglycemia in diabetes might be due at least in part to up-regulation of megsin which can inhibit plasmin and MMP activities.

Original languageEnglish
Pages (from-to)768-774
Number of pages7
JournalKidney international
Volume74
Issue number6
DOIs
Publication statusPublished - 2008 Sep

Keywords

  • Diabetic glomerulosclerosis
  • Matrix metalloproteinase
  • Megsin
  • Mesangial extracellular matrix
  • Plasmin

ASJC Scopus subject areas

  • Nephrology

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