PI-3 kinase pathway can mediate the effect of TGF-β1 in inducing the expression of SHARP-2 in LLC-PK1 cells

作     者：Zhang-fei SHOU Qin ZHOU Jie-ru CAI Jiang-hua CHEN Kazuya YAMADA Kaoru MIYAMOTO 

作者机构：Kidney Disease Center the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China Key Laboratory of Multi-organ Combined Transplantation Ministry of Health Hangzhou 310003 China Department of Biochemistry Faculty of Medical Sciences University of Fukui Eiheiji-cho Fukui 910-1193 Japan 

出 版 物：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报（英文版）B辑（生物医学与生物技术）)

年 卷 期：2009年第10卷第9期

页      面：702-706页

核心收录：

学科分类：071010[理学-生物化学与分子生物学] 03[法学] 081704[工学-应用化学] 030107[法学-经济法学] 07[理学] 08[工学] 0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 0301[法学-法学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 0905[农学-畜牧学] 0817[工学-化学工程与技术] 0906[农学-兽医学] 

基　　金：supported by the National Natural Science Foundation of China (Nos. 30471641 and 30872389) the Natural Science Foundation of Zhejiang Province, China (No. Y207088) 

主　　题：转化生长因子 有限责任公司 信号转导通路 细胞系 夏普 激酶 PI 诱导 

摘      要：We aim to investigate the effect of transforming growth factor (TGF)-β1 on the expression of enhancer of split- and hairy-related protein-2 (SHARP-2) messenger RNA (mRNA) and its signaling pathway. In this study, several cell lines including LLC-PK1 (a porcine kidney tubular epithelial cell line), MDCK (Madin-Darby canine kidney) and CTLL-2 (cytotoxic T-lymphocyte line) were treated with recombinant human TGF-β1, and a series of experiments were carried out, involving Northern blot analysis of total RNA from these cells. Further, several specific chemical inhibitors were applied before TGF-β1 treatment to probe the signaling pathway. The results showed that TGF-β1 can significantly up-regulate SHARP-2 mRNA expression in the LLC-PK1 cell line. The peak level of induction was found 2 h after TGF-β1 stimulation. While one phospho-inositide 3-kinases (PI-3) kinase inhibitor, LY294002, completely blocked the effect of TGF-β1 on SHARP-2 mRNA expression in LLC-PK1 cells at a low concentration, other inhibitors, including PD98059, staurosporine, AG490, wortmannin, okadaic acid and rapamycin, had no effect. The effect of LY294002 was dose-dependent. We conclude that, in LLC-PK1 cells at least, TGF-β1 can effectively induce the SHARP-2 mRNA expression and that the PI-3 kinase pathway can mediate this effect.