Sav1 loss induces senescence and Stat3 activation coinciding with tubulointerstitial fibrosis

Janet Y. Leung, Harper L. Wilson, Kristin J. Voltzke, Lindsay A. Williams, Hyo Jin Lee, Sara E. Wobker, William Y. Kim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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

Original languageEnglish (US)
Article numbere00565-16
JournalMolecular and cellular biology
Volume37
Issue number12
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 American Society for Microbiology.

Keywords

  • Fibrosis
  • Mouse
  • Renal
  • Senescence

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