Inhibition of TRPM7 Attenuates Rat Aortic Smooth Muscle Cell Proliferation Induced by Angiotensin II: Role of Genistein
Inhibition of TRPM7 Attenuates Rat Aortic Smooth Muscle Cell Proliferation Induced by Angiotensin II: Role of Genistein
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抑制 TRPM7 可减弱血管紧张素 II 诱导的大鼠主动脉平滑肌细胞增殖：金雀异黄酮的作用
DOI：
10.1097/fjc.0000000000000238
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发表时间：
2015
影响因子：
3
通讯作者：
Liming Zhang
中科院分区：
文献类型：
--
作者：
Meimei Yang;T. Zhao;Jinghan Lin;Ting Ju;Liming Zhang
摘要：瞬时受体电位melastatin 7（TRPM 7）是TRP通道超家族中的一种Ca 2+、Mg 2+可渗透的非选择性阳离子通道，在细胞生长和增殖中发挥重要作用。改变通道蛋白的活性和表达的化合物可能具有治疗意义。本研究探讨了染料木素对大鼠主动脉平滑肌细胞（RAoSMCs）TRPM 7通道及增殖的影响。在原代培养的RAoSMC中，急性染料木素（50 M）暴露抑制天然TRPM 7电流，而慢性暴露染料木素（50 M）下调TRPM 7蛋白表达。染料木素诱导TRPM 7蛋白表达的下调被c-Src抑制剂（PP 2）模仿，但不被表皮生长因子受体酪氨酸激酶抑制剂（laveustin A）或大豆苷元。此外，染料木黄酮（50 M）衰减血管紧张素II诱导的细胞增殖。本研究首次证明了在RAoSMC中，通过c-Src酪氨酸激酶抑制，异黄酮抑制TRPM 7。我们的研究结果不仅提供了一个新的TRPM 7的调节机制，而且还表明TRPM 7可能作为染料木素治疗血管疾病的一个新的治疗靶点。
Abstract: Transient receptor potential melastatin 7 (TRPM7) is a Ca2+, Mg2+ permeable nonselective cation channel of the TRP channel superfamily and plays an important role in cell growth and proliferation. Compounds that alter the activity and expression of the channel protein might be of therapeutic interest. In this study, we investigated the effects of genistein on TRPM7 channels and the proliferation of rat aortic smooth muscle cells (RAoSMCs). In primary cultured RAoSMCs, acute genistein (50 &mgr;M) exposure inhibited native TRPM7 currents, whereas chronic expose to genistein (50 &mgr;M) downregulated TRPM7 protein expression. The downregulation of TRPM7 protein expression induced by genistein was mimicked by c-Src inhibitor (PP2), but not by epidermal growth factor receptor tyrosine kinase inhibitor (lavendustin A), or daidzein. Additionally, genistein (50 &mgr;M) attenuated angiotensin II–induced cell proliferation. This study is the first to demonstrate inhibition of TRPM7 by isoflavone genistein through c-Src tyrosine kinase inhibition in RAoSMCs. Our results not only provide a new modulation mechanism of TRPM7 but also suggest that TRPM7 may serve as a new therapeutic target of genistein in the treatment of vascular diseases.
影响因子：
3.6
作者：
Belevych, AE;Warrier, S;Harvey, RD
通讯作者：
Harvey, RD
DOI：
10.1016/j.bbamcr.2014.04.019
发表时间：
2014-09
影响因子：
5.1
作者：
Sun, Yuyang;Sukumaran, Pramod;Varma, Archana;Derry, Susan;Sahmoun, Abe E.;Singh, Brij B.
通讯作者：
Singh, Brij B.
影响因子：
6
作者：
Barnes, S;Boersma, B;Xu, J
通讯作者：
Xu, J