Eur Rev Med Pharmacol Sci 2020; 24 (12): 7039-7050

DOI: 10.26355/eurrev_202006_21697

Exosome-mediated miR-106a-3p derived from ox-LDL exposed macrophages accelerated cell proliferation and repressed cell apoptosis of human vascular smooth muscle cells

Y. Liu, W.-L. Zhang, J.-J. Gu, Y.-Q. Sun, H.-Z. Cui, J.-Q. Bu, Z.-Y. Chen

Department of Cardiac Surgery, Second Hospital of Hebei Medical University, Shi Jiazhuang, China. chenziying1964@163.com


OBJECTIVE: Atherosclerosis (AS) is a leading disease with high mortality and morbidity in the world. It has been demonstrated that exosomes can transfer some miRNAs or proteins to regulate the biological functions of human vascular smooth muscle cells (VSMCs) and promote the progression of AS. In this study, we mainly aimed at exploring potential functions of exosomes derived from ox-LDL exposed macrophages and investigating the potential mechanisms of exosome-mediated miR-106a-3p in regulating VSMCs and promoting AS.

MATERIALS AND METHODS: Ox-LDL was used to treat THP-1 macrophages, CCK-8 assay was performed to detect cell viability, and flow cytometric analysis was used to detect cell apoptosis. Exosomes were isolated and collected with centrifugation, and were determined by transmission electron microscopy and WB assay. RT-PCR was used to detect the expressions of miRNAs in exosomes and VSMCs, WB assay was used to detect protein expressions. MiR-106a-3p mimic was transfected into VSMCs to verify its functions and the Luciferase gene reporter assay was performed to prove the binding site of miR-106a-3p and CASP9. Finally, GW4869, an inhibitor for exosome secretion, was used to block exosome secretion by ox-LDL induced THP-1 and to confirm the effects of miR-106a-3p on cell proliferation and apoptosis in VSMCs.

RESULTS: We found that ox-LDL induced THP-1 could promote cell proliferation and repress cell apoptosis of VSMCs, then, exosomes were successfully isolated, which could promote cell proliferation and repressed cell apoptosis of VSMCs after adding into VSMCs. Furthermore, we found that miR-106a-3p was significantly increased in exosomes from ox-LDL induced THP-1 and its expression was also increased in VSMCs after adding into VSMCs. Moreover, miR-106a-3p overexpression could promote cell viability and repress cell apoptosis, as well as regulate associated protein expressions. Additionally, the Luciferase gene reporter assay confirmed that miR-106a-3p could directly bind with CASP9 and regulate Caspase signaling in VSMCs. Finally, blocking exosomes from ox-LDL induced THP-1 reduced the cell viability and promoted cell apoptosis in VSMCs.

CONCLUSIONS: Above all, this study demonstrated that miR-106a-3p was increased in exosomes from ox-LDL induced THP-1 and it could promote cell proliferation and repress cell apoptosis of VSMCs. We found that the exosomes-mediated miR-106a-3p could directly bind with CASP9 and repress Caspase signaling pathway in VSMCs, which might provide a potential target for treating AS.

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Y. Liu, W.-L. Zhang, J.-J. Gu, Y.-Q. Sun, H.-Z. Cui, J.-Q. Bu, Z.-Y. Chen
Exosome-mediated miR-106a-3p derived from ox-LDL exposed macrophages accelerated cell proliferation and repressed cell apoptosis of human vascular smooth muscle cells

Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 12
Pages: 7039-7050
DOI: 10.26355/eurrev_202006_21697