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Updated: Mar 6, 2026

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Sav1 Loss Induces Senescence and Stat3 Activation Coinciding with Tubulointerstitial Fibrosis

Janet Y Leung1,2, Harper L Wilson3, Kristin J Voltzke3,4

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA janet_leung@med.unc.edu wykim@med.unc.edu.

Molecular and Cellular Biology
|March 22, 2017
PubMed

Insights

Loss of Sav1 in mouse kidneys causes tubulointerstitial fibrosis (TIF) by activating Stat3 and senescence. YAP inhibitor verteporfin (VP) blocked fibrosis, suggesting VP as a potential treatment for chronic kidney disease (CKD).

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathology

Background:

  • Tubulointerstitial fibrosis (TIF) is a key factor in chronic kidney disease (CKD) progression to end-stage renal disease (ESRD).
  • The molecular mechanisms driving TIF are not fully understood, highlighting the need for further research into fibrotic pathways.

Purpose of the Study:

  • To investigate the role of Sav1 in renal tubulointerstitial fibrosis.
  • To explore the potential of YAP inhibition as a therapeutic strategy for TIF.

Main Methods:

  • Conditional inactivation of the Sav1 gene in mouse renal epithelium.
  • Analysis of gene expression, Stat3 activation, and senescence-associated secretory phenotype (SASP).
  • Treatment with the YAP inhibitor verteporfin (VP) to assess its effects on fibrosis.

Main Results:

  • Conditional Sav1 inactivation in renal epithelium upregulated profibrotic genes and induced TIF.
  • Loss of Sav1 activated Stat3 and promoted a SASP, correlating with fibrosis development.
  • Verteporfin treatment inhibited senescence-related gene activation, Stat3, and SASP, thereby impeding fibrosis.

Conclusions:

  • Sav1 deficiency in renal epithelium drives TIF through Stat3 activation and SASP.
  • YAP inhibition with verteporfin shows promise in preventing or treating TIF.
  • These findings offer new insights into fibrosis mechanisms and identify VP as a potential therapeutic agent for CKD and TIF.
Keywords:
fibrosismouserenalsenescence

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