Inhibition of Podocyte FAK Protects against Proteinuria and Foot Process Effacement
Inhibition of Podocyte FAK Protects against Proteinuria and Foot Process Effacement
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DOI：
10.1681/asn.2009090991
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发表时间：
2010-07-01
影响因子：
13.6
通讯作者：
Ishibe, Shuta
中科院分区：
文献类型：
--
作者：
Ma, Hong;Togawa, Akashi;Ishibe, Shuta
粘着斑激酶（FAK）是一种非受体酪氨酸激酶，在细胞运动中起关键作用。足细胞足突的运动和收缩，伴随足细胞损伤，提示局灶性粘连解体。为了更好地了解足细胞足突消失导致蛋白尿和肾功能衰竭的机制，我们研究了足细胞中FAK的功能。在小鼠模型中，肾小球损伤导致足细胞FAK活化，随后出现蛋白尿和足突消失。足细胞特异性FAK缺失和FAK药物失活均能消除肾小球损伤引起的蛋白尿和足突消失。在体外，从条件性FAK敲除小鼠中分离的足细胞表现出扩散和迁移减少; FAK的药理学失活对野生型足细胞具有类似的作用。总之，FAK激活调节足细胞足突消失，表明药物抑制这种信号级联反应可能具有治疗肾小球损伤的潜力。
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.