TY - JOUR
T1 - Inhibition of podocyte FAK protects against proteinuria and foot process effacement
AU - Ma, Hong
AU - Togawa, Akashi
AU - Soda, Keita
AU - Zhang, Junhui
AU - Lee, Sik
AU - Ma, Ming
AU - Yu, Zhiheng
AU - Ardito, Thomas
AU - Czyzyk, Jan
AU - Diggs, Lonnette
AU - Joly, Dominique
AU - Hatakeyama, Shinji
AU - Kawahara, Eiji
AU - Holzman, Lawrence
AU - Guan, Jun Lin
AU - Ishibe, Shuta
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2009090991
DO - 10.1681/ASN.2009090991
M3 - Article
C2 - 20522532
AN - SCOPUS:77954599877
SN - 1046-6673
VL - 21
SP - 1145
EP - 1156
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 7
ER -