Activation of renal renin-angiotensin system in upstream stimulatory factor 2 transgenic mice

Lihua Shi, Dejan Nikolic, Shu Liu, Hong Lu, Shuxia Wang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Previously we demonstrated that upstream stimulatory factor 2 (USF2) transgenic (Tg) mice developed nephropathy including albu-minuria and glomerular hypertrophy, accompanied by increased transforming growth factor (TGF)-β and fibronectin accumulation in the glomeruli. However, the mechanisms by which overexpression of USF2 induces kidney injury are unknown. USF has been shown to regulate renin expression. Moreover, the renin-angiotensin system (RAS) plays important roles in renal diseases. Therefore, in the present studies the effects of USF2 on the regulation of RAS in the kidney as well as in mesangial cells from USF2 (Tg) mice were examined. The role of USF2-mediated regulation of RAS in TGF-β production in mesangial cells was also determined. Our data demonstrate that USF2 (Tg) mice exhibit increased renin and angiotensin (ANG) II levels in the kidney. In contrast, renal expression of other components of RAS such as renin receptor, angiotensinogen, angio-tensin-converting enzyme (ACE), ACE2, angiotensin type 1a (AT1a) receptor, and AT2 receptor was not altered in USF2 (Tg) mice. Similarly, mesangial cells isolated from USF2 (Tg) mice had increased renin and ANG II levels. Mesangial cells overexpressing USF2 also had increased TGF-β production, which was blocked by small interfering RNA-mediated renin gene knockdown or RAS blockade (enalapril or losartan). Collectively, these results suggest that USF2 promotes renal renin expression and stimulates ANG II generation, leading to activation of the intrarenal RAS. In addition, renin-dependent ANG II generation mediates the effect of USF2 on TGF-β production in mesangial cells, which may contribute to the development of nephropathy in USF2 (Tg) mice.

Original languageEnglish
Pages (from-to)F257-F265
JournalAmerican Journal of Physiology - Renal Physiology
Issue number2
StatePublished - Feb 2009


  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Urology


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