Homer binds to Orai1 and TRPC channels in the neointima and regulates vascular smooth muscle cell migration and proliferation.
Homer binds to Orai1 and TRPC channels in the neointima and regulates vascular smooth muscle cell migration and proliferation.
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DOI：
10.1038/s41598-017-04747-w
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发表时间：
2017-07-11
影响因子：
4.6
通讯作者：
Yuan JP
中科院分区：
文献类型：
--
作者：
Jia S;Rodriguez M;Williams AG;Yuan JP
增殖和迁移血管平滑肌细胞（VSMC）中钙池操纵的Ca 2+内流通道（SOC）的分子组成非常复杂，有许多通道参与SOC。它们包括Ca 2+选择性Orai 1和瞬时受体电位经典（TRPC）通道的成员，这些通道由内质网Ca 2+传感器STIM 1激活。支架蛋白Homer组装SOC复合物，但其在VSMCs中的作用还不清楚。在这里，我们询问这些SOC组分和Homer 1是否存在于VSMC中的同一复合物中，以及Homer 1如何促进VSMC SOC、增殖和迁移，从而导致新生内膜形成。Homer 1表达水平在球囊损伤与未损伤的VSMC中上调。免疫共沉淀试验揭示了所有SOC组分在受损VSMC中的存在和相互作用，其中Homer 1与Orai 1和各种TRPC通道相互作用。因此，敲低培养的VSMC中的Homer 1部分抑制SOC、VSMC迁移和VSMC增殖。用表达针对Homer 1 mRNA的短发夹RNA的腺相关病毒载体（AAV-shHomer 1）治疗后，新生内膜面积减少。这些发现强调了多种钙离子内流通道在VSMCs中的作用，并首次显示了Homer蛋白在VSMCs中的作用及其在新生内膜形成中的重要性。
The molecular components of store-operated Ca2+ influx channels (SOCs) in proliferative and migratory vascular smooth muscle cells (VSMCs) are quite intricate with many channels contributing to SOCs. They include the Ca2+-selective Orai1 and members of the transient receptor potential canonical (TRPC) channels, which are activated by the endoplasmic reticulum Ca2+ sensor STIM1. The scaffolding protein Homer assembles SOC complexes, but its role in VSMCs is not well understood. Here, we asked whether these SOC components and Homer1 are present in the same complex in VSMCs and how Homer1 contributes to VSMC SOCs, proliferation, and migration leading to neointima formation. Homer1 expression levels are upregulated in balloon-injured vs. uninjured VSMCs. Coimmunoprecipitation assays revealed the presence and interaction of all SOC components in the injured VSMCs, where Homer1 interacts with Orai1 and various TRPC channels. Accordingly, knockdown of Homer1 in cultured VSMCs partially inhibited SOCs, VSMC migration, and VSMC proliferation. Neointimal area was reduced after treatment with an adeno-associated viral vector expressing a short hairpin RNA against Homer1 mRNA (AAV-shHomer1). These findings stress the role of multiple Ca2+ influx channels in VSMCs and are the first to show the role of Homer proteins in VSMCs and its importance in neointima formation.
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影响因子：
3.5
作者：
Balasuriya, Dilshan;Srivats, Shyam;Edwardson, J. Michael
通讯作者：
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影响因子：
5.3
作者：
Sala, C;Roussignol, G;Fagni, L
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Worley, Paul F.
DOI：
10.1073/pnas.1118947109
发表时间：
2012-04-10
影响因子：
11.1
作者：
Yang, Xue;Jin, Hao;Shen, Yuequan
通讯作者：
Shen, Yuequan