Inhibition of podocyte FAK protects against proteinuria and foot process effacement

Hong Ma, Akashi Togawa, Keita Soda, Junhui Zhang, Sik Lee, Ming Ma, Zhiheng Yu, Thomas Ardito, Jan Czyzyk, Lonnette Diggs, Dominique Joly, Shinji Hatakeyama, Eiji Kawahara, Lawrence Holzman, Jun Lin Guan, Shuta Ishibe

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that plays a critical role in cell motility. Movement and retraction of podocyte foot processes, which accompany podocyte injury, suggest focal adhesion disassembly. To understand better the mechanisms by which podocyte foot process effacement leads to proteinuria and kidney failure, we studied the function of FAK in podocytes. In murine models, glomerular injury led to activation of podocyte FAK, followed by proteinuria and foot process effacement. Both podocyte-specific deletion of FAK and pharmacologic inactivation of FAK abrogated the proteinuria and foot process effacement induced by glomerular injury. In vitro, podocytes isolated from conditional FAK knockout mice demonstrated reduced spreading and migration; pharmacologic inactivation of FAK had similar effects on wild-type podocytes. In conclusion, FAK activation regulates podocyte foot process effacement, suggesting that pharmacologic inhibition of this signaling cascade may have therapeutic potential in the setting of glomerular injury.

Original languageEnglish (US)
Pages (from-to)1145-1156
Number of pages12
JournalJournal of the American Society of Nephrology
Volume21
Issue number7
DOIs
StatePublished - Jul 2010

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