The Study of Progressive Factors to Developing Glomerular Injury

点击翻译按钮获取中文摘要

Mesangial cell proliferation is a general characteristic of a variety of glomerular injuries. Growth arrest gene 6 (Gas 6) was one of vitamin K-dependent proteins, which was reported that the γ-carboxylation of Gas 6 is essential for its receptor-binding and growth-promoting activities in cells. The present study shows the role of Gas 6 for development of glomerular injury. Gas 6 is a new autocrine growth factor of mesangial cells. We examined the role of Gas 6/Axl in vivo in an experimental anti-Thy1 glomerulonephritis. The expression of Gas 6 was markedly increased in glomeruli in the model and the administration of warfarin significantly inhibited mesangial proliferation and the increased Gas 6 expression. The administration of Axl-extracellular domain (receptor for Gas 6) also inhibited mesangial cell proliferation. Gas 6 induced mesangial cell proliferation via latent transcription factor STAT3 in vitro and in vivo. To investigate these findings, we constructed Gas 6-/- mice and examined the role of it in accelerated nephrotoxic nephritis. Gas 6-/- mice showed less proteinuria, glomerular cell proliferation, glomerulosvlerosis and crescent formation than wild-type nephritis. These data indicate that Gas 6 contributes to glomerular injury and the progression of glomerular sclerosis.