High glucose upregulates upstream stimulatory factor 2 in human renal proximal tubular cells through angiotensin II-dependent activation of CREB

Nishant P. Visavadiya, Yanzhang Li, Shuxia Wang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background/Aims: We have previously demonstrated that a transcription factor, upstream stimulatory factor 2 (USF2), regulates glucose-induced thrombospondin 1 expression and transforming growth factor-β activity in mesangial cells, and plays an important role in diabetic glomerulopathy. In this study, we determined whether USF2 expression in renal proximal tubular cells is regulated by glucose and contributes to diabetic tubulointerstitial fibrosis. Methods: Human renal proximal tubular cells (HK-2 cells) were treated with normal- or high-glucose medium for 24 h. After treatment, real-time PCR or immunoblotting was used to determine the expression of USF2 and other components of the renin-angiotensin system in HK-2 cells. Results: High glucose upregulated USF2 expression and increased extracellular matrix accumulation in HK-2 cells; both were inhibited by siRNA-mediated USF2 knockdown. In addition, high glucose stimulated angiotensinogen and renin expression, increased renin activity, and resulted in increased angiotensin II formation. Treatment of HK-2 cells with an angiotensin II receptor 1 (AT1) blocker - losartan - prevented high-glucose-induced USF2 expression and high-glucose-enhanced phosphorylation of CREB (cAMP response element-binding protein). Conclusion: Our data established that high glucose stimulated USF2 expression in HK-2 cells, at least in part, through angiotensin II-AT1-dependent activation of CREB, which can contribute to diabetic tubulointerstitial fibrosis.

Original languageEnglish
Pages (from-to)e62-e70
JournalNephron - Experimental Nephrology
Volume117
Issue number3
DOIs
StatePublished - Feb 2011

Keywords

  • CREB
  • High glucose
  • Renal proximal tubular cells
  • Renin-angiotensin system
  • Upstream stimulatory factor 2
  • cAMP response element-binding protein (CREB)

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Nephrology

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