Inhibitor of DNA Binding 1 Is Induced during Kidney Ischemia-Reperfusion and Is Critical for the Induction of Hypoxia-Inducible Factor-1α

Biomed Res Int. 2016:2016:4634386. doi: 10.1155/2016/4634386. Epub 2016 Apr 5.

Abstract

In this study, rat models of acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) and HK-2 cell models of hypoxia-reoxygenation (H/R) were established to investigate the expression of inhibitor of DNA binding 1 (ID1) in AKI, and the regulation relationship between ID1 and hypoxia-inducible factor 1 alpha (HIF-1α). Through western blot, quantitative real-time PCR, immunohistochemistry, and other experiment methods, the induction of ID1 after renal I/R in vivo was observed, which was expressed mainly in renal tubular epithelial cells (TECs). ID1 expression was upregulated in in vitro H/R models at both the protein and mRNA levels. Via RNAi, it was found that ID1 induction was inhibited with silencing of HIF-1α. Moreover, the suppression of ID1 mRNA expression could lead to decreased expression and transcription of HIF-1α during hypoxia and reoxygenation. In addition, it was demonstrated that both ID1 and HIF-1α can regulate the transcription of twist. This study demonstrated that ID1 is induced in renal TECs during I/R and can regulate the transcription and expression of HIF-1α.

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / pathology
  • Animals
  • Cell Hypoxia / genetics
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression
  • Gene Silencing
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Inhibitor of Differentiation Protein 1 / biosynthesis*
  • Inhibitor of Differentiation Protein 1 / genetics
  • Kidney Tubules, Distal / metabolism*
  • Kidney Tubules, Distal / pathology
  • RNA, Messenger / biosynthesis
  • Rats
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / pathology

Substances

  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • ID1 protein, rat
  • Inhibitor of Differentiation Protein 1
  • RNA, Messenger