Institute for Cardiovascular & Metabolic Diseases, University of North Texas Health Sciences Center, Fort Worth, TX, 76107, USA.
Sci Rep. 2017 Jul 11;7(1):5075. doi: 10.1038/s41598-017-04747-w.
The molecular components of store-operated Ca influx channels (SOCs) in proliferative and migratory vascular smooth muscle cells (VSMCs) are quite intricate with many channels contributing to SOCs. They include the Ca-selective Orai1 and members of the transient receptor potential canonical (TRPC) channels, which are activated by the endoplasmic reticulum Ca 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 Ca influx channels in VSMCs and are the first to show the role of Homer proteins in VSMCs and its importance in neointima formation.
储存操作型钙内流通道（SOCs）的分子成分在增殖和迁移的血管平滑肌细胞（VSMCs）中非常复杂，许多通道都有助于 SOCs 的形成。它们包括钙选择性 Orai1 和瞬时受体电位经典（TRPC）通道成员，它们被内质网钙传感器 STIM1 激活。支架蛋白 Homer 组装 SOC 复合物，但它在 VSMCs 中的作用尚不清楚。在这里，我们想知道这些 SOC 成分和 Homer1 是否存在于 VSMCs 中的同一个复合物中，以及 Homer1 如何有助于 VSMC SOCs、增殖和迁移，从而导致新生内膜形成。与未受伤的 VSMCs 相比，受伤的 VSMCs 中 Homer1 的表达水平上调。共免疫沉淀分析显示，受伤的 VSMCs 中存在所有 SOC 成分的相互作用，其中 Homer1 与 Orai1 和各种 TRPC 通道相互作用。因此，在培养的 VSMCs 中敲低 Homer1 会部分抑制 SOCs、VSMC 迁移和 VSMC 增殖。用表达针对 Homer1 mRNA 的短发夹 RNA 的腺相关病毒载体（AAV-shHomer1）治疗后，新生内膜面积减少。这些发现强调了多种钙内流通道在 VSMCs 中的作用，并且是首次表明 Homer 蛋白在 VSMCs 中的作用及其在新生内膜形成中的重要性。
