Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy

Background Urotensin If (UII) is an 11-amino acid vasoactive peptide, recently identified as the ligand for a novel G protein-coupled receptor, GPR-14 (renamed urotensin receptor [UT]). In addition to its potent vasoconstrictive actions, UII also has trophic and profibrotic effects, leading to its implication in the pathogenesis of heart failure. However, elevated plasma UII levels also were reported in association with renal impairment and diabetes. Accordingly, the present study sought to examine the expression and localization of UII and its receptor in kidney tissue from patients with diabetic nephropathy. Methods.-We quantified UII and UT gene expression in renal biopsy tissue samples from patients with diabetic nephropathy by using quantitative real-time polymerase chain reaction and determined the intrarenal distribution of their peptides by means of immunohistochemistry. Results: In human diabetic tissue, gene expression of UII and UT were increased 45- and almost 2,000-fold in comparison to control nephrectomy tissue, respectively (P < 0.0001). Immunohistochemical studies showed intense UII peptide staining in diabetic tissue localized predominantly to tubular epithelial cells, and fluorescein-labeled ligand binding studies showed a similar tubular pattern of distribution. Conclusion: In the context of its known biological actions, the dramatic overexpression of UII and its receptor implicate this vasoactive peptide as a possible novel factor in the pathogenesis of diabetic nephropathy.