The role and molecular mechanism of Urotensin II in renal disease: focus on tubular injury and renal fibrosis Urotensin II (UII) is a cyclic vasoactive peptide expressed in multiple organs. The kidney appears to be a major source of both circulating and urinary UII. UII is found in the proximal renal tubules and collecting ducts. Studies investigated effects of UII on renal function yielded conflicting results with increase or decrease of glomerular filtration rate and natriuresis.Whether UII has a causative or protective influence on renal disease remains to be dertermined. UII is elevated in the circulation or urine of patients with renal failure, including a higher urinary level of UII in patients with renal tubular disorders. The expression of UII and UT receptor is also increased in the tubular epithelial cells of patients with diabetic nephropaty. The causal relationship of UII in renal tubular injury is not yet identified, although UII may play an important role of these diseases. Unilateral ureteric obstruction (UUO) model has been intensively used as it leads to stress induced tubular cell apoptosis and eventually progresses to tubulointerstitial fibrosis. This model presents a good system to explore the mechanism of tubular injury and renal fibrosis which was a common feature of renal failure. Therefore in this 3-year proposal, we will construct an in vitro system mimicking UUO and use in vivo rat UUO model to investigate the role and molecular mechanism of UII in renal disease, especially focus on renal tubular injury and renal fibrosis. By examining the expression pattern with plasma and urine level of UII in UUO rat, and correlating with tissue pathological and relative tissue injury marker changes, we can evaluate the potential of UII as a biomarker for renal disease. By establishing the experimental cell model imitating UUO animal condition, we can identify the eliciting stress and the signaling pathway involved in UII induction in renal tubular cells. The influence of UII on stress-induced injury and its molecular mechanism will also be checked. Finally, we will observe the effect of UII treatment in UUO rat model. This study will offer us the understanding of UII on renal disease, whether it is protective or causative, and examining the therapeutic potential of UII on renal failure.
|Effective start/end date||8/1/10 → 7/31/11|
- urotensin II
- renal disease
- tubular injury
- renal fibrosis
- unilateral ureteric obstruction