Open AccessRole of urotensin II in advanced glycation end product-induced extracellular matrix synthesis in rat proximal tubular epithelial cells
Author(s) -
Lin Tian,
Peng Fu,
Min Zhou,
Yue Gu,
Yunqian Li,
Jiping Qi
Publication year - 2016
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2016.2789
Subject(s) - urotensin ii , extracellular matrix , fibronectin , glycation , microbiology and biotechnology , secretion , extracellular , chemistry , medicine , endocrinology , biology , biochemistry , receptor , diabetes mellitus
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.