Effects of norepinephrine‑induced activation of rat vascular adventitial fibroblasts on proliferation and migration of BMSCs involved in vascular remodeling

去甲肾上腺素诱导的大鼠血管外膜成纤维细胞活化对参与血管重塑的骨髓间充质干细胞增殖和迁移的影响

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作者:Jun Gao, Li Li, Dongli Zhou, Xuhong Sun, Lilu Cui, Donglin Yang, Xiaohui Wang, Pengchao Du, Wendan Yuan

Abstract

Vascular remodeling caused by vascular injury such as hypertension and atherosclerosis is a complex process involving a variety of cells and factors, and the mechanism is unclear. A vascular injury model was simulated by adding norepinephrine (NE) to culture medium of vascular adventitial fibroblasts (AFs). NE induced activation and proliferation of AFs. To investigate the association between the AFs activation and bone marrow mesenchymal stem cells (BMSCs) differentiation in vascular remodeling. BMSCs were cultured with supernatant of the AFs culture medium. BMSC differentiation and migration were observed by immunostaining and Transwell assay, respectively, while cell proliferation was measured using the Cell Counting Kit-8. Expression levels of smooth muscle actin (α-SMA), TGF-β1 and SMAD3 were measured using western blot assay. The results indicated that compared with those in the control group, in which BMSCs were cultured in normal medium, expression levels of α-SMA, TGF-β1 and SMAD3 in BMSCs cultured in medium supplemented with supernatant of AFs, increased significantly (all P<0.05). Activated AFs induced the differentiation of BMSCs into vascular smooth muscle-like cells and promoted proliferation and migration. AFs activated by NE may induce BMSCs to participate in vascular remodeling. These findings may help design and develop new approaches and therapeutic strategies for vascular injury to prevent pathological remodeling.

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