Partial endothelial-to-mesenchymal transition (EndMT) contributes to lumen re-organization after carotid artery ligation
Partial endothelial-to-mesenchymal transition (EndMT) contributes to lumen re-organization after carotid artery ligation
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DOI：
10.1101/2021.08.13.456319
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发表时间：
2021-08
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影响因子：
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通讯作者：
Yoshito Yamashiro;K. Ramírez;K. Nagayama;S. Tomita;Y. Kubota;H. Yanagisawa
中科院分区：
文献类型：
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作者：
Yoshito Yamashiro;K. Ramírez;K. Nagayama;S. Tomita;Y. Kubota;H. Yanagisawa
内皮-间质转化（EndMT）是血管重塑的基本过程。颈动脉结扎通常用于诱导新内膜形成和血管狭窄；然而，血管重塑的精确调节机制尚不完全清楚。在这项研究中，我们发现常驻内皮细胞（EC）是新内膜细胞的起源，并且EC在新内膜形成的早期阶段短暂表达CD45，并伴随着EndMT标记物的表达增加。在体外，用氯化钴或VHL抑制剂稳定HIF-1α，在人原代EC中诱导CD45阳性EndMT，模拟结扎动脉的缺氧条件，并促进整合素α11-SHARPIN复合物的形成。值得注意的是，CD45 磷酸酶抑制剂破坏了该复合物，从而破坏了细胞与细胞连接的稳定性。这些结果表明，CD45 活性是 EndMT（称为“部分 EndMT”）期间 EC 表型和细胞-细胞连接的保留所必需的。因此，我们提出了一种新的部分 EndMT 机制，有助于血管损伤期间的管腔重组。
Endothelial-to-mesenchymal transition (EndMT) is a fundamental process in vascular remodeling. Carotid artery ligation is commonly used for induction of neointima formation and vessel stenosis; however, the precise regulatory mechanism of vascular remodeling is not entirely understood. In this study, we showed that resident endothelial cells (ECs) are the origin of neointima cells and ECs transiently expressed CD45 in the early stage of neointima formation accompanied by increased expression of EndMT markers. In vitro, CD45-positive EndMT was induced by stabilization of HIF-1α with cobalt chloride or VHL inhibitor in human primary ECs, which mimicked the hypoxic condition of ligated artery, and promoted the formation of integrin α11-SHARPIN complex. Notably, a CD45 phosphatase inhibitor disrupted this complex, thereby destabilizing cell-cell junctions. These results suggest that the CD45 activity is required for the retention of an EC phenotype and cell-cell junctions during EndMT (termed “partial EndMT”). We thus propose a novel mechanism of partial EndMT that contributes to lumen re-organization during vascular injury.