International Journal of Clinical and Experimental Pathology | |
A crosstalk triggered by hypoxia and maintained by MCP-1/miR-98/IL-6/p38 regulatory loop between human aortic smooth muscle cells and macrophages leads to aortic smooth muscle cells apoptosis via Stat1 activation | |
Qing Wang1  | |
关键词: Abdominal aortic aneurysm; MCP-1; hypoxia; IL-6; macrophage; | |
DOI : | |
学科分类:生理学与病理学 | |
来源: e-Century Publishing Corporation | |
【 摘 要 】
Hypoxia and inflammation are central characteristics of the abdominal aortic aneurysm (AAA), but the mechanisms for their relationship and actual role remain far from full understood. Here, we showed MCP-1 (monocyte chemotactic protein-1) induced by hypoxia in primary human Aortic Smooth Muscle Cells (hASMCs) increased the chemotaxis of THP-1 macrophages and MCP-1 induced IL-6 expression in THP-1 cells via downregulating miR-98 which directly targets IL-6. In addition, IL-6 positively feedback regulated MCP-1 expression in hASMCs via p38 signal that is independent on hypoxia, and inhibition of p38 signal blocked the effect of IL-6 on MCP-1 expression regulation. Moreover, IL-6 exposure time-dependently induces phASMCs apoptosis via Stat1 activation. Collectively, our data provide compelling evidence on the association between hypoxia and inflammation triggered by hypoxia and then mediated by MCP-1/miR-98/IL-6/p38 regulatory loop, which leads to hASMCs apoptosis via Stat1 activation to contribute to AAA formation and progression.
【 授权许可】
CC BY-NC
【 预 览 】
Files | Size | Format | View |
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RO201901234662082ZK.pdf | 1584KB | download |