High glucose levels upregulate upstream stimulatory factor 2 gene transcription in mesangial cells

Lihua Shi, Shu Liu, Dejan Nikolic, Shuxia Wang

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Previously, we demonstrated that upstream stimulatory factor 2 (USF2) mediates high glucose-induced thrombospondin1 (TSP1) gene expression and TGF-β activity in glomerular mesangial cells and plays a role in diabetic renal complications. In the present studies, we further determined the molecular mechanisms by which high glucose levels regulate USF2 gene expression. In primary rat mesangial cells, we found that glucose treatment time and dose-dependently upregulated USF2 expression (mRNA and protein). By using cycloheximide to block the de novo protein synthesis, similar rate of USF2 degradation was found under either normal glucose or high glucose conditions. USF2 mRNA stability was not altered by high glucose treatment. Furthermore, high glucose treatment stimulated USF2 gene promoter activity. By using the luciferase-promoter deletion assay, site-directed mutagenesis, and transactivation assay, we identified a glucose-responsive element in the USF2 gene promoter (-1,740 to -1,620, relative to the transcription start site) and demonstrated that glucose-induced USF2 expression is mediated through a cAMP-response element-binding protein (CREB)-dependent transactivation of the USF2 promoter. Furthermore, siRNA-mediated CREB knock down abolished glucose-induced USF2 expression. Taken together, these data indicate that high glucose levels upregulate USF2 gene transcription in mesangial cells through CREB-dependent transactivation of the USF2 promoter.

Original languageEnglish
Pages (from-to)1952-1961
Number of pages10
JournalJournal of Cellular Biochemistry
Issue number6
StatePublished - Apr 15 2008


  • Gene transcription
  • Glucose
  • Mesangial cells
  • USF2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'High glucose levels upregulate upstream stimulatory factor 2 gene transcription in mesangial cells'. Together they form a unique fingerprint.

Cite this