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Loss of focal adhesion kinase activation in podocytes protects mice from proteinuria and foot process effacement

Ma, Hong and Togawa, Akashi and Soda, Keita and Zhang, Junhui and Lee, Sik and Ma, Ming and Yu, Zhiheng and Ardito, Thomas and Czyzyk, Jan and Diggs, Lonnette and Joly, Dominique and Hatakeyama, Shinji and Kawahara, Eiji and Holzman, Lawrence B. and Guan, Jun Lin and Ishibe, Shuta (2010) Loss of focal adhesion kinase activation in podocytes protects mice from proteinuria and foot process effacement. Journal of the American Society of Nephrolgy, 21 (7). pp. 1145-1156.

Abstract

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that plays a critical role in cell motility. Podocyte foot process effacement leads to proteinuria and kidney failure, but the mechanisms are not fully understood, limiting therapeutic options currently available. In this study, we examined the role and implications of FAK in podocytes. We found that in murine models of glomerular injury, podocytes demonstrated robust FAK activation and subsequent proteinuria and foot process effacement. However, mice lacking FAK selectively in podocytes were resistant to proteinuria and foot process effacement. Consistent with the hypothesis that loss of FAK reduces cell movement, analysis of podocytes isolated from the conditional FAK knockout mice, demonstrated reduced migration with the diminution of MMP-2 activity. Pharmacological inactivation of FAK also resulted in decreased cell migration in-vitro, as well as diminished proteinuria and foot process effacement in vivo. Together, our results provide evidence that FAK activation regulates podocyte foot process effacement, and inhibiting this signaling cascade may serve as a target for therapeutic interventions.

Item Type: Article
Date Deposited: 13 Oct 2015 13:17
Last Modified: 13 Oct 2015 13:17
URI: https://oak.novartis.com/id/eprint/1256

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