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Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells
- Title
- Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells
- Authors
- Kim, Yerin; Yu, Namhee; Jang, Ye Eun; Lee, Eunkyung; Jung, Yeonjoo; Lee, Doo Jae; Taylor, W. Robert; Jo, Hanjoong; Kim, Jaesang; Lee, Sanghyuk; Kang, Sang Won
- Ewha Authors
- 이상혁; 강상원; 김재상; 이두재; 정연주
- SCOPUS Author ID
- 이상혁; 강상원; 김재상; 이두재; 정연주
- Issue Date
- 2023
- Journal Title
- SCIENTIFIC REPORTS
- ISSN
- 2045-2322
- Citation
- SCIENTIFIC REPORTS vol. 13, no. 1
- Publisher
- NATURE PORTFOLIO
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Endothelial dysfunction and inflammatory immune response trigger dedifferentiation of vascular smooth muscle cells (SMCs) from contractile to synthetic phenotype and initiate arterial occlusion. However, the complex vascular remodeling process playing roles in arterial occlusion initiation is largely unknown. We performed bulk sequencing of small and messenger RNAs in a rodent arterial injury model. Bioinformatic data analyses reveal that six miRNAs are overexpressed in injured rat carotids as well as synthetic-type human vascular SMCs. In vitro cell-based assays show that four miRNAs (miR-130b-5p, miR-132-3p, miR-370-3p, and miR-410-3p) distinctly regulate the proliferation of and monocyte adhesion to the vascular SMCs. Individual inhibition of the four selected miRNAs strongly prevents the neointimal hyperplasia in the injured rat carotid arteries. Mechanistically, miR-132-3p and miR-370-3p direct the cell cycle progression, triggering SMC proliferation. Gene ontology analysis of mRNA sequencing data consistently reveal that the miRNA targets include gene clusters that direct proliferation, differentiation, and inflammation. Notably, bone morphogenic protein (BMP)-7 is a prominent target gene of miR-370-3p, and it regulates vascular SMC proliferation in cellular and animal models. Overall, this study first reports that the miR-370-3p/BMP-7 axis determines the vascular SMC phenotype in both rodent and human systems.
- DOI
- 10.1038/s41598-022-26711-z
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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