STAT1 and STAT3 mediate thrombin-induced expression of TIMP-1 in human glomerular mesangial cells

Kidney International
Xiangmei ChenZhiheng Yu

Abstract

Thrombin exhibits numerous biological effects on glomerular resident cells, such as cell proliferation, release and synthesis of cytokines and collagen, expressions of metalloproteinases and their inhibitors, especially tissue inhibitor of metalloproteinase-1 (TIMP-1). However, the signaling mechanisms underlying these cellular events have not been fully elucidated. The present study was designed to examine the role of signal transducers and activators of transcription (STAT) in thrombin-induced TIMP-1 expression in human mesangial cells. Cultured human glomerular mesangial cells were incubated with thrombin up to 12 hours. The effects of the antisense of STAT1 and antisense of STAT3 on stimulated TIMP-1 mRNA levels and DNA-binding activities of both STAT1 and STAT3 were determined using Northern blot, electrophoretic mobility shift assay (EMSA), and supershift assay. Cultured human mesangial cells constitutively expressed TIMP-1, and thrombin induced TIMP-1 gene transcription in a time- and dose-dependent manner. Hirudin, a specific inhibitor of thrombin, could block thrombin-induced TIMP-1 expression. Thrombin also induced STAT-DNA binding activity in a similar time- and dose-dependent manner. In order to examine the role of ...Continue Reading

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Citations

Mar 10, 2005·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Wuxing ZhangQuan Hong
Dec 22, 2007·Nephron. Experimental Nephrology·Jianzhong WangQuan Hong
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Jun 11, 2005·World Journal of Gastroenterology : WJG·Atsushi MasamuneTooru Shimosegawa

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