Irisin is induced in renal ischemia-reperfusion to protect against tubular cell injury via suppressing p53

Yuxue Liu, Ying Fu, Zhiwen Liu, Shaoqun Shu, Ying Wang, Juan Cai, Chengyuan Tang, Zheng Dong

Research output: Contribution to journalArticle

Abstract

Renal ischemia-reperfusion is a major cause of acute kidney injury, a disease currently without effective treatments. Irisin was initially identified as an important factor produced by muscles to mediate the health benefits of exercise, and recent work has further suggested its protective effect against lung and liver injury. However, the role of Irisin in kidney diseases, including renal ischemia-reperfusion injury (IRI), remains unknown. In the present study, we found that the Irisin precursor, fibronectin type III domain-containing protein 5 (Fndc5), was induced in renal tubules in a mouse model of renal IRI and in cultured mouse renal proximal tubular cells subjected ATP depletion injury. Functionally, silencing Fndc5 in cultured proximal tubular cells increased the sensitivity to ATP depletion-induced apoptosis, whereas both Fndc5 overexpression and supplementation of recombinant Irisin alleviated ATP depletion-induced apoptosis. In vivo, administration of recombinant Irisin dramatically attenuated kidney dysfunction, tissue damage, tubular cell apoptosis, and inflammation during renal IRI in mice. Mechanistically, Irisin suppressed the activation of p53 in renal IRI, a critical factor in tubular cell death. Together, these results indicate that Irisin is induced in renal IRI as a protective mechanism for renal tubular cells, suggesting the therapeutic potential of recombinant Irisin in renal IRI and related kidney diseases.

Original languageEnglish (US)
Article number165792
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • Acute kidney injury
  • Apoptosis
  • Irisin
  • Renal ischemia-reperfusion
  • p53

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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