tPA is a potent mitogen for renal interstitial fibroblasts: role of beta1 integrin/focal adhesion kinase signaling.

The American Journal of Pathology
Sha HaoYouhua Liu

Abstract

Proliferation and expansion of interstitial fibroblasts are predominant features of progressive chronic kidney diseases. However, how interstitial fibroblast proliferation is controlled remains ambiguous. Here we show that tissue-type plasminogen activator (tPA) is a potent mitogen that promotes interstitial fibroblast proliferation through a cascade of signaling events. In vitro, tPA promoted cell proliferation of rat kidney fibroblasts (NRK-49F), as assessed by cell counting, cell proliferation assay, and bromodeoxyuridine labeling. tPA also accelerated NRK-49F cell cycle progression. Fibroblast proliferation induced by tPA was associated with an increased expression of numerous proliferation-related genes, including c-fos, c-myc, proliferating cell nuclear antigen, and cyclin D1. The mitogenic effect of tPA was independent of its protease activity, but required LDL receptor-related protein 1. Interestingly, inhibition of beta1 integrin signaling prevented tPA-mediated fibroblast proliferation. tPA rapidly induced tyrosine phosphorylation of focal adhesion kinase (FAK), which led to activation of its downstream mitogen-activated protein kinase signaling. Blockade of FAK, but not integrin-linked kinase, abolished the tPA-trigg...Continue Reading

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Citations

Oct 20, 2011·Nature Reviews. Nephrology·Youhua Liu
Oct 13, 2011·The Journal of Biological Chemistry·Zuguo LiShi-You Chen
Apr 12, 2012·American Journal of Physiology. Renal Physiology·Roderick J Tan, Youhua Liu
Aug 6, 2011·Journal of the American Society of Nephrology : JASN·Sha HaoYouhua Liu
Jul 8, 2011·Kidney International·Inga SörensenRoland Schmitt
Nov 29, 2013·Kidney International·Kai SongLi-Fang Hu
Sep 11, 2016·Journal of the American Society of Nephrology : JASN·Haiyan FuYouhua Liu
Oct 12, 2018·American Journal of Physiology. Renal Physiology·Eoghainín Ó hAinmhireBenjamin D Humphreys
May 11, 2013·Journal of the American Society of Nephrology : JASN·Lei JiangChunsun Dai
Nov 14, 2014·Journal of the American Society of Nephrology : JASN·Jun AiFan Fan Hou
Apr 20, 2014·Journal of the American Society of Nephrology : JASN·Dong ZhouYouhua Liu

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