血管生成
整合素
细胞生物学
巨噬细胞
整合素连接激酶
生物
癌症研究
免疫学
细胞
激酶
蛋白激酶A
体外
生物化学
细胞周期蛋白依赖激酶2
作者
Ruoshui Li,Bijun Chen,Akihiko Kubota,Anis Hanna,Claudio Humeres,Silvia C Hernandez,Yang Liu,Rong Ma,Izabela Tuleta,Shuaibo Huang,Harikrishnan Venugopal,Fang Zhu,Kai Su,Jun Li,Jinghang Zhang,Deyou Zheng,Nikolaos G. Frangogiannis
标识
DOI:10.1038/s41467-023-43369-x
摘要
Abstract Macrophages sense changes in the extracellular matrix environment through the integrins and play a central role in regulation of the reparative response after myocardial infarction. Here we show that macrophage integrin α5 protects the infarcted heart from adverse remodeling and that the protective actions are associated with acquisition of an angiogenic macrophage phenotype. We demonstrate that myeloid cell- and macrophage-specific integrin α5 knockout mice have accentuated adverse post-infarction remodeling, accompanied by reduced angiogenesis in the infarct and border zone. Single cell RNA-sequencing identifies an angiogenic infarct macrophage population with high Itga5 expression. The angiogenic effects of integrin α5 in macrophages involve upregulation of Vascular Endothelial Growth Factor A. RNA-sequencing of the macrophage transcriptome in vivo and in vitro followed by bioinformatic analysis identifies several intracellular kinases as potential downstream targets of integrin α5. Neutralization assays demonstrate that the angiogenic actions of integrin α5-stimulated macrophages involve activation of Focal Adhesion Kinase and Phosphoinositide 3 Kinase cascades.
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