Susceptibility of renal fibrosis in diabetes: Role of hypoxia inducible factor-1

Shuqin Mei, Lin Li, Xiangjun Zhou, Cheng Xue, Man J. Livingston, Qingqing Wei, Bing Dai, Zhiguo Mao, Changlin Mei, Zheng Dong

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Diabetes may prevent kidney repair and sensitize the kidney to fibrosis or scar formation. To test this possibility, we examined renal fibrosis induced by unilateral ureteral obstruction (UUO) in diabetic mouse models. Indeed, UUO induced significantly more renal fibrosis in both Akita and STZ-induced diabetic mice than in nondiabetic mice. The diabetic mice also had more apoptosis and interstitial macrophage infiltration during UUO. In vitro, hypoxia induced higher expression of the fibrosis marker protein fibronectin in high glucose-conditioned renal tubular cells than in normal glucose cells. Mechanistically, hypoxia induced significantly more hypoxia-inducible factor-1 α (HIF-1 α) in high glucose cells than in normal glucose cells. Inhibition of HIF-1 attenuated the expression of fibronectin induced by hypoxia in high-glucose cells. Consistently, UUO induced significantly higher HIF-1α expression along with fibrosis in diabetic mice kidneys than in nondiabetic kidneys. The increased expression of fibrosis induced by UUO in diabetic mice was diminished in proximal tubule-HIF-1α-knockout mice. Together, these results indicate that diabetes sensitizes kidney tissues and cells to fibrogenesis probably by enhancing HIF-1 activation.

Original languageEnglish (US)
Article numbere22477
JournalFASEB Journal
Volume36
Issue number8
DOIs
StatePublished - Aug 2022

Keywords

  • HIF-1
  • diabetic kidney disease
  • fibrosis
  • high glucose

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'Susceptibility of renal fibrosis in diabetes: Role of hypoxia inducible factor-1'. Together they form a unique fingerprint.

Cite this