Heme oxygenase-1 ameliorates kidney ischemia-reperfusion injury in mice through extracellular signal-regulated kinase 1/2-enhanced tubular epithelium proliferation

Hsin Hung Chen, Pei Jung Lu, Bo Ron Chen, Michael Hsiao, Wen Yu Ho, Ching Jiunn Tseng

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Heme oxygenase (HO)-1 confers transient resistance against oxidative damage, including renal ischemia-reperfusion injury (IRI). We investigated the potential protective effect of HO-1 induction in a mouse model of renal IRI induced by bilateral clamping of the kidney arteries. The mice were randomly assigned to five groups to receive an intraperitoneal injection of PBS, hemin (an HO-1 inducer, 100. μmol/kg), hemin + ZnPP (an HO-1 inhibitor, 5 mg/kg), hemin + PD98059 (a MEK-ERK inhibitor, 10. mg/kg) or a sham operation. All of the groups except for the sham-operated group underwent 25. min of ischemia and 24 to 72. h of reperfusion. Renal function and tubular damage were assessed in the mice that received hemin or the vehicle treatment prior to IRI. The renal injury score and HO-1 protein levels were evaluated via H&E and immunohistochemistry staining. Hemin-preconditioned mice exhibited preserved renal cell function (BUN: 40 ± 2 mg/dl, creatinine: 0.53 ± 0.06. mg/dl), and the tubular injury score at 72 h (1.65 ± 0.12) indicated that tubular damage was prevented. Induction of HO-1 induced the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2. However, these effects were abolished with ZnPP treatment. Kidney function (BUN: 176 ± 49 mg/dl, creatinine: 1.54 ± 0.39 mg/dl) increased, and the tubular injury score (3.73 ± 0.09) indicated that tubular damage also increased with ZnPP treatment. HO-1-induced tubular epithelial proliferation was attenuated by PD98059. Our findings suggest that HO-1 preconditioning promotes ERK1/2 phosphorylation and enhances tubular recovery, which subsequently prevents further renal injury.

Original languageEnglish
Pages (from-to)2195-2201
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

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