1. Academic Validation
  2. Essential role of Gas6 for glomerular injury in nephrotoxic nephritis

Essential role of Gas6 for glomerular injury in nephrotoxic nephritis

  • J Clin Invest. 2002 Jul;110(2):239-46. doi: 10.1172/JCI14861.
Motoko Yanagita 1 Yoshikazu Ishimoto Hidenori Arai Kojiro Nagai Tsuyoshi Ito Toru Nakano David J Salant Atsushi Fukatsu Toshio Doi Toru Kita
Affiliations

Affiliation

  • 1 Department of Geriatric Medicine, Kyoto University, Kyoto, Japan.
Abstract

Growth-arrest specific gene 6 (Gas6) is a vitamin K-dependent growth factor for mesangial and epithelial cells. To investigate whether Gas6 is essential for progressive glomerular injury, we constructed Gas6(-/-) mice and examined the role of Gas6 in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis. We found less mortality and proteinuria in Gas6(-/-) mice than in wild-type mice following injection of nephrotoxic serum. Glomerular cell proliferation, glomerular sclerosis, crescent formation, and deposition of fibrin/fibrinogen in glomeruli were also reduced in Gas6(-/-) mice. Furthermore, administering Gas6(-/-) mice recombinant wild-type Gas6, but not Gas6 lacking a previously characterized N-terminal gamma-carboxyl group, induced massive proteinuria, glomerular cell proliferation, and glomerulosclerosis, comparable to responses seen in wild-type mice. These data indicate that Gas6 induces glomerular cell proliferation in NTN and suggest that this factor contributes to glomerular injury and the progression of chronic nephritis.

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