title: Urotensin II induces transactivation of the epidermal growth factor receptor via transient oxidation of SHP-2 in the rat renal tubular cell line NRK-52E.
abstract: Urotensin-II (UII) is a potent vasoactive peptide that has been implicated in cardiac fibrosis and renal diseases. However, the role played by UII in renal tissues is largely unknown. In this study, we investigated the effects of human UII (hUII) on rat renal proximal tubular cells of the NRK-52E line and the role of Src homology 2-containing phosphotyrosine phosphatase (SHP-2) in the hUII-induced transactivation of the epidermal growth factor receptor (EGFR). Exposure to hUII at low concentrations significantly induced proliferation in NRK-52E cells; this effect was inhibited by treatment with an ERK1/2 inhibitor (PD98059). UII treatment increased the phosphorylation of EGFR and induced the generation of reactive oxygen species (ROS). Treatment of the ROS scavenger N-acetyl-cysteine (NAC) inhibited EGFR transactivation and ERK phosphorylation induced by hUII. SHP-2 was found to interact with EGFR and be transiently oxidized following the hUII treatment. In SHP-2 knockdown cells, UII-induced phosphorylation of EGFR was less influenced by NAC, and significantly suppressed by heparin binding (HB)-EGF neutralizing antibody. Our data suggest that the ROS-mediated oxidation of SHP-2 is essential for the hUII-induced mitogenic pathway in NRK-52E cells.
authors.affiliation: Division of Nephrology, Taipei Medical University-Wan Fang Hospital, Taipei City, Taiwan, Republic of China.
authors.forename: Yuh-Mou
authors.initials: YM
authors.lastname: Sue
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Chen
authors.forename: Yung-Ho
authors.initials: YH
authors.lastname: Hsu
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Hou
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Cheng
authors.forename: Yen-Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Shih-Li
authors.initials: SL
authors.lastname: Lin
authors.forename: Tzen-Wen
authors.initials: TW
authors.lastname: Chen
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen