Sav1 Loss Induces Senescence and Stat3 Activation Coinciding with Tubulointerstitial Fibrosis

• DOI: 10.1128/mcb.00565-16
• Publication Date: 2017-03-21T00:25:33Z
• Authors: Janet Y. Leung; Harper L. Wilson; Kristin J. Voltzke; Lindsay A. Williams; Hyo Jin Lee; Sara E. Wobker; William Y. Kim
• Keywords: Senescence

ABSTRACT Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal (ESRD). Here we show that conditional inactivation of Sav1 mouse epithelium resulted upregulated expression profibrotic genes and TIF. Loss induced Stat3 activation senescence-associated secretory phenotype (SASP) coincided with development tubulointerstitial fibrosis. Treatment mice YAP inhibitor verteporfin (VP) inhibited associated senescence, SASPs, well impeded Collectively, our studies offer novel insights into molecular events are linked loss implicate VP potential pharmacological treat patients at risk for developing CKD