Increased expression of p21WAF1/CIP1 in kidney proximal tubules mediates fibrosis

Judit Megyesi, Adel Tarcsafalvi, Shenyang Li, Rawad Hodeify, Nang San Hti Lar Seng, Didier Portilla, Peter M. Price

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Tissue fibrosis is a major cause of death in developed countries. It commonly occurs after either acute or chronic injury and affects diverse organs, including the heart, liver, lung, and kidney. Using the renal ablation model of chronic kidney disease, we previously found that the development of progressive renal fibrosis was dependent on p21WAF1/Cip1 expression; the genetic knockout of the p21 gene greatly alleviated this disease. In the present study, we expanded on this observation and report that fibrosis induced by two different acute injuries to the kidney is also dependent on p21. In addition, when p21 expression was restricted only to the proximal tubule, fibrosis after injury was induced in the whole organ. One molecular fibrogenic switch we describe is transforming growth factor-β induction, which occurred in vivo and in cultured kidney cells exposed to adenovirus expressing p21. Our data suggests that fibrosis is p21 dependent and that preventing p21 induction after stress could be a novel therapeutic target.

Original languageEnglish
Pages (from-to)F122-F130
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume308
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

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Keywords

  • Cyclin-dependent kinase inhibitor 1A
  • Fibrosis
  • p21
  • Proximal tubule
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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