Research ArticlePhysiology

YAP-mediated mechanotransduction determines the podocyte’s response to damage

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Sci. Signal.  11 Apr 2017:
Vol. 10, Issue 474, eaaf8165
DOI: 10.1126/scisignal.aaf8165

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A target for preventing kidney damage

In the kidney glomerulus, the elaborate foot processes of podocytes form the filtration barrier through which water, salts, and waste products pass into the urine. Proteinuria, or the appearance of protein in the urine, results when these cells or their foot processes are damaged. Using a rat model of chemically induced acute nephrosis, Rinschen et al. found that the activation of the transcriptional coactivator YAP and the expression of YAP target genes preceded proteinuria. YAP activity can be stimulated by mechanical stress, and activation of YAP in cultured podocytes depended on the stiffness of the substrate, implying that fibrosis may affect how podocytes respond to damage. Experiments in rats suggested that inhibiting YAP activity may be beneficial for patients with certain types of kidney diseases.