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Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells.


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.

SUBMITTER: Kim Y 

PROVIDER: S-EPMC9918535 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells.

Kim Yerin Y   Yu Namhee N   Jang Ye Eun YE   Lee Eunkyung E   Jung Yeonjoo Y   Lee Doo Jae DJ   Taylor W Robert WR   Jo Hanjoong H   Kim Jaesang J   Lee Sanghyuk S   Kang Sang Won SW  

Scientific reports 20230210 1


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 w  ...[more]

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