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

Yerin Kim, Namhee Yu, Ye Eun Jang, Eunkyung Lee, Yeonjoo Jung, Doo Jae Lee, W. Robert Taylor, Hanjoong Jo, Jaesang Kim, Sanghyuk Lee, Sang Won Kang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number2404
JournalScientific Reports
Volume13
Issue number1
DOIs
StatePublished - Dec 2023

Bibliographical note

Funding Information:
We thank the Dr. Jiyong Jang and mouse facility members for technical support. This study was supported by grants from the National Research Foundation of Korea (2017M3A9G2077885).

Publisher Copyright:
© 2023, The Author(s).

Fingerprint

Dive into the research topics of 'Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells'. Together they form a unique fingerprint.

Cite this