Cyclin D1 activation through ATF-2 in Reg-induced pancreatic beta-cell regeneration.
Cyclin D1 activation through ATF-2 in Reg-induced pancreatic beta-cell regeneration.
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发表时间：
2006
期刊：
影响因子：
3.5
通讯作者：
S. Takasawa;T. Ikeda;T. Akiyama;K. Nata;K. Nakagawa;N. Shervani;N. Noguchi;Shoko Murakami-Kawaguchi;A. Yamauchi;I. Takahashi;T. Tomioka-Kumagai;H. Okamoto
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作者：
S. Takasawa;T. Ikeda;T. Akiyama;K. Nata;K. Nakagawa;N. Shervani;N. Noguchi;Shoko Murakami-Kawaguchi;A. Yamauchi;I. Takahashi;T. Tomioka-Kumagai;H. Okamoto
再生基因产物(REG)在胰岛β细胞中被诱导，作为一种自分泌/旁分泌生长因子，通过细胞表面的REG受体进行再生。然而，REG诱导β细胞再生的方式尚不清楚。在本研究中，我们发现Reg增加了磷酸化的ATF-2，它与细胞周期蛋白D1基因的-57到-52结合来激活启动子。PI(3)K抑制剂LY294002和Wortmannin可减弱Reg/ATF-2诱导的细胞周期蛋白D1启动子的激活。在REG基因敲除的小鼠胰岛中，磷酸化ATF-2、细胞周期蛋白D1和磷酸化Rb的水平显著降低。这些结果表明，Reg-Reg受体系统刺激PI(3)K/ATF-2/Cyclin D1信号通路，诱导β细胞再生。
Regenerating gene product (Reg) is induced in pancreatic beta-cells and acts as an autocrine/paracrine growth factor for regeneration via a cell surface Reg receptor. However, the manner by which Reg induces beta-cell regeneration was unknown. In the present study, we found that Reg increased phospho-ATF-2, which binds to -57 to -52 of the cyclin D1 gene to activate the promoter. The Reg/ATF-2-induced cyclin D1 promoter activation was attenuated by PI(3)K inhibitors such as LY294002 and wortmannin. In Reg knockout mouse islets, the levels of phospho-ATF-2, cyclin D1, and phospho-Rb were greatly decreased. These results indicate that the Reg-Reg receptor system stimulates the PI(3)K/ATF-2/cyclin D1 signaling pathway to induce beta-cell regeneration.