Endoplasmic reticulum stress is activated in post-ischemic kidneys to promote chronic kidney disease

Shaoqun Shu, Jiefu Zhu, Zhiwen Liu, Chengyuan Tang, Juan Cai, Zheng Dong

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background: Acute kidney injury (AKI) may lead to the development of chronic kidney disease (CKD), i.e. AKI-CKD transition, but the underlying mechanism remains largely unclear. Endoplasmic reticulum (ER) stress is characterized by the accumulation of unfolded or misfolded proteins in ER resulting in a cellular stress response. The role of ER stress in AKI-CKD transition remains unknown. Methods: In this study, we examined ER stress in the mouse model of AKI-CKD transition after unilateral renal ischemia-reperfusion injury (uIR). To determine the role of ER stress in AKI-CKD transition, we tested the effects of two chemical chaperones: Tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid (4-PBA). Findings: uIR led to the induction of ER stress in kidneys, as indicated by increased expression of UPR molecules CHOP (C/EBP homologous protein) and BiP(binding immunoglobulin protein; also called GRP78–78 kDa glucose­regulated protein). Given at 3 days after uIR, both TUDCA and 4-PBA blocked ER stress in post-ischemic kidneys. Notably, both chemicals promoted renal recovery and suppressed tubulointerstitial injury as manifested by the reduction of tubular atrophy, renal fibrosis and myofibroblast activation. Inhibition of ER stress further attenuated renal tubular epithelial cell apoptosis, inflammation and autophagy in post-ischemic kidneys. Interpretation: These findings suggest that ER stress contributes critically to the development of chronic kidney pathologies and CKD following AKI, and inhibition of ER stress may represent a potential therapeutic strategy to impede AKI-CKD transition.

Original languageEnglish (US)
Pages (from-to)269-280
Number of pages12
JournalEBioMedicine
Volume37
DOIs
StatePublished - Nov 2018

Keywords

  • AKI-CKD transition
  • Apoptosis
  • Autophagy
  • ER stress
  • Fibrosis
  • Renal ischemia-reperfusion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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