Abstract
Our previous study demonstrated in vivo that mouse cytomegalovirus (MCMV) infection promoted vascular remodeling after downregulation of miR-1929-3p. This study aimed to investigate the role of miR-1929-3p/ETAR/NLRP3 pathway in mouse vascular smooth muscle cells (MOVAS) after MCMV infection. First, PCR was used to detect the success of the infection. Second, MOVAS were transfected with the miR-1929-3p mimic, inhibitor, and ETAR overexpressed adenovirus vector. Cell proliferation was detected using EdU, whereas apoptosis was detected using flow cytometry. The expression of miR-1929-3p and ETAR were detected using qRT-PCR. Western blot detected proteins of cell proliferation, apoptosis, and the NLRP3 inflammasome. Interleukin-1β and interleukin-18 were determined using ELISA. The results revealed that after 48 h, MCMV infection promoted the proliferation of MOVAS when the MOI was 0.01. MCMV infection increased ETAR by downregulating miR-1929-3p. The miR-1929-3p mimic reversed the proliferation and apoptosis, whereas the miR-1929-3p inhibitor promoted this effect. ETAR overexpression further promoted MCMV infection by downregulating miR-1929-3p-mediated proliferation and apoptosis. MCMV infection mediates the downregulation of miR-1929-3p and the upregulation of ETAR, which activates NLRP3 inflammasome. In conclusion, MCMV infection promoted the proliferation of MOVAS, possibly by downregulating miR-1929-3p, promoting the upregulation of the target gene ETAR and activating NLRP3 inflammasome.
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Abbreviations
- MCMV:
-
Mouse cytomegalovirus
- MOVAS:
-
Mouse vascular smooth muscle cells
- VSMCs:
-
Vascular smooth muscle cells
- miRNA:
-
MicroRNA
- ETAR:
-
Endothelin receptor type A
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Funding
The present study was supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant No. 2020-PT330-003), the grants from the National Natural Science Foundation of China (Grant No. 31960187), the National College Students innovation and Entrepreneurship training program (Grant No. 202010759027), the Scientific research project of Shihezi University (Grant No. ZZZC201921A), the “3152” project of Shihezi University (Grant No. ZG010308), and the Youth Innovation and Talent Cultivation project of Shihezi University (grant NO.CXPY202216).
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He, L., Zhou, W., Wang, L. et al. Murine Cytomegalovirus Infection Induced miR-1929-3p Down-Regulation Promotes the Proliferation and Apoptosis of Vascular Smooth Muscle Cells in Mice by Targeting Endothelin A Receptor and Downstream NLRP3 Activation Pathway. Mol Biotechnol 65, 1954–1967 (2023). https://doi.org/10.1007/s12033-023-00720-3
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DOI: https://doi.org/10.1007/s12033-023-00720-3