Role of urotensin II in advanced glycation end product-induced extracellular matrix synthesis in rat proximal tubular epithelial cells

Abstract

Urotensin II (UII) was first recognized for its constrictive and natriuretic properties in fish almost 40 years ago, and recent studies have suggested that it exerts pro-fibrotic effects in a number of cell lines. In this study, we aimed to evaluate the role of UII in extracellular matrix (ECM) synthesis and secretion in advanced glycation end product (AGE)-stimulated rat proximal tubular epithelial cells (NRK-52E cells). UII promoted the proliferation of the NRK-52E cells in a dose-dependent manner over a concentration range of 10-10-10-8 mol/l and this effect was partly inhibited by both nimodipine and EDTA. Furthermore, AGE-BSA promoted the mRNA and protein expression of UII, fibronectin (FN) and collagen IV (ColIV) in the NRK-52E cells in a dose- and time-dependent manner. In addition, UII promoted the mRNA expression and protein secretion of transforming growth factor (TGF)-β1, FN and Col IV by the NRK-52E cells. Our results suggest that UII promotes the proliferation of NRK-52E cells, an effect which is mediated by the influx of extracellular calcium ions. In addition, our data indicate that AGEs promote UII expression in NRK-52E cells, and that TGF-β1 signaling is a candidate pathway mediating the involvement of UII in renal fibrosis. Collectively, our data suggest that the UII-TGF-β1 signaling may be an important factor in tubulointerstitial nephropathy in diabetes.

Urotensin II-induced store-operated Ca2+ entry contributes to glomerular mesangial cell proliferation and extracellular matrix protein production under high glucose conditions

“…Immunofluorescence staining of type IV collagen and fibronectin also indicated that UII stimulates their production by individual cells. These data are consistent with studies that reported an increase in fibronectin and collagen mRNA expression in rat proximal tubular epithelial cells and cardiac fibroblasts treated with UII 42 , 43 . Thus, a combination of increased proliferation and synthesis by individual GMCs may account for UII-induced ECM accumulation.…”

Effects of Thymoquinone on Urotensin-II and TGF-β1 Levels in Model of Osteonecrosis in Rats

“…To elucidate the mechanisms underlying the multiple protective effects of TMQ, we evaluated the levels of TGF-β1 and U-II using ELISA. Studies in the literature have shown that TGF-β1 and UT-II have many biological activities in processes such as proliferation, fibrosis, and inflammation [9,46]. As shown in Figure 1 of our study, TMQ treatment given after MPA-induced ON development significantly reduced fatty degeneration, osteonecrosis, 4-HNE, and 8-OHdG levels.…”

Astragaloside IV alleviates renal fibrosis by inhibiting renal tubular epithelial cell pyroptosis induced by urotensin II through regulating the cAMP/PKA signaling pathway

“…In the kidney, the expression of GPR14 is most abundant in distal convoluted tubules, collecting duct epithelial cells, and glomerular capillary endothelial cells [27]. Some studies have found that UII combined with GPR14 can exert biological effects such as vasoconstriction, cell proliferation, and extracellular matrix expression and secretion [28][29][30], regulate inflammatory signaling pathways such as JAK2/STAT3 by inducing the production of pro-fibrotic factors such as TGF-β1 [31], and involved in the occurrence and development of renal fibrosis [32]. These studies suggested that UII is the key factor leading to renal fibrosis.…”