Role of SUMOylation of STAT1 in tubular epithelial‑mesenchymal transition induced by high glucose

Mol Med Rep. 2023 Feb;27(2):42. doi: 10.3892/mmr.2023.12929. Epub 2023 Jan 5.

Abstract

Tubulointerstitial fibrosis (TIF) is an important pathological change that occurs during the development of diabetic kidney disease. The epithelial‑mesenchymal transition (EMT) of renal tubular epithelial cells is a manifestation of TIF. STAT1, a member of the STAT family of transcription factors, can be modified by the small ubiquitin‑related modifier (SUMO), thus affecting the activity of STAT1. The present study investigated the role of STAT1 SUMOylation in high glucose‑induced tubular EMT by western blotting, immunocytochemistry, immunofluorescence, co‑immunoprecipitation and dual luciferase reporter analysis. The results indicated that in the process of high glucose‑induced EMT, STAT1 activation protected the cells from EMT. However, high glucose also increased the SUMOylation of STAT1, which prevented STAT1 from exerting an effective protective role by inhibiting its activity.

Keywords: STAT1; epithelial‑mesenchymal transition; high glucose; renal tubular epithelial cells; small ubiquitin‑related modifier.

MeSH terms

  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition*
  • Fibrosis
  • Glucose / pharmacology
  • Humans
  • STAT1 Transcription Factor / metabolism
  • Sumoylation*
  • Transcription Factors

Substances

  • Transcription Factors
  • Glucose
  • STAT1 protein, human
  • STAT1 Transcription Factor

Grants and funding

This study was supported by the National Natural Science Foundation (grant nos. 81600564, 81800623 and 21605035), the Hebei Natural Science Foundation (grant nos. H2020206262 and H2019206045), and the Department of Health of Hebei Province (grant no. 20180044).