Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cells.
Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cells.
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DOI：
10.1038/ki.2008.403
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发表时间：
2008-12
影响因子：
19.6
通讯作者：
King, George L.
中科院分区：
文献类型：
--
作者：
Isshiki, Keiji;He, Zhiheng;Maeno, Yasuhiro;Ma, Ronald C.;Yasuda, Yutaka;Kuroki, Tatsuya;White, Gregory S.;Patti, Mary E.;Weir, Gordon C.;King, George L.
肾脏肥大和细胞外基质蛋白沉积是糖尿病肾病的一致发现，这些过程可以通过血糖正常控制来停止或逆转。利用基因芯片技术对糖尿病大鼠和正常大鼠肾小球RNA进行分析，发现糖尿病大鼠肾小球胰岛素样生长因子1受体（IGF-1 R）的表达水平升高，而细胞因子信号抑制因子2（SOCS 2）和STAT 5的表达水平降低。所有这些变化均通过胰岛细胞移植恢复正常。SOCS 2在大鼠系膜细胞中的过表达抑制IGF-1诱导的细胞外信号调节激酶的活化，其随后减少IV型胶原和DNA合成，这是由于SOCS 2与IGF-1 R的相互作用而产生的效果。通过小干扰RNA抑制SOCS 2过表达通过阻止p66 Shc衔接蛋白中酪氨酸317的磷酸化来抑制IGF-1 R介导的作用;然而，SOCS 1或SOCS 3的过表达并不影响IGF-1 R信号传导。胰岛素直接增加系膜细胞STAT 5和SOCS 2的表达。本研究表明，胰岛素可通过调节STAT 5/SOCS 2的表达来抑制IGF-1在系膜细胞中的促有丝分裂作用。胰岛素缺乏可能通过减少STAT 5/SOCS 2表达而导致糖尿病中发现的系膜扩张。
Renal hypertrophy and deposition of extracellular matrix proteins are consistent findings in diabetic nephropathy and these processes can be halted or reversed by euglycemic control. Using DNA microarray analysis of glomerular RNA from control and diabetic rats we found that the expression levels of insulin-like growth factor 1 receptor (IGF-1R) were increased while those of suppressor of cytokine signaling 2 (SOCS2) and STAT5 were decreased. All of these changes were normalized by islet cell transplantation. Overexpression of SOCS2 in rat mesangial cells inhibited IGF-1-induced activation of extracellular signal-regulated kinase, which subsequently reduced type IV collagen and DNA synthesis, an effect due to interaction of SOCS2 with IGF-1R. Inhibition of SOCS2 overexpression by small interfering RNA suppressed IGF-1R-mediated actions by preventing phosphorylation of tyrosine 317 in the p66Shc adaptor protein; however, overexpression of either SOCS1 or SOCS3 did not affect IGF-1R signaling. Insulin directly increased STAT5 and SOCS2 expression in mesangial cells. This study shows that insulin can inhibit the mitogenic action of IGF-1 in mesangial cells by regulating STAT5/SOCS2 expression. Insulin deficiency may contribute to the mesangial expansion found in diabetes through reduced STAT5/SOCS2 expression.
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影响因子：
7.7
作者：
Mahadevan, P;Larkins, RG;Dunlop, ME
通讯作者：
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DOI：
10.1152/ajpgi.00413.2004
发表时间：
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