title: 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.
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Fu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Qi
mesh_terms: D000818:Animals; D015415:Biomarkers; D049109:Cell Proliferation; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014579:Urotensins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D024141:Collagen Type IV; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D053773:Transforming Growth Factor beta1; D014579:Urotensins; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; C029677:urotensin II