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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26711-z |
| _version_ | 1811165958856769536 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yerin Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T15:44:36Z |
| format | Article |
| id | doaj.art-c77127ba599e4589abbe5b3faa047b1b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T15:44:36Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c77127ba599e4589abbe5b3faa047b1b2023-02-12T12:12:32ZengNature PortfolioScientific Reports2045-23222023-02-0113111410.1038/s41598-022-26711-zConserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cellsYerin Kim0Namhee Yu1Ye Eun Jang2Eunkyung Lee3Yeonjoo Jung4Doo Jae Lee5W. Robert Taylor6Hanjoong Jo7Jaesang Kim8Sanghyuk Lee9Sang Won Kang10Department of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityDivision of Cardiology, Emory University School of MedicineWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityDepartment of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityAbstract 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.https://doi.org/10.1038/s41598-022-26711-z |
| spellingShingle | 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 Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells Scientific Reports |
| title | Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells |
| title_full | Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells |
| title_fullStr | Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells |
| title_full_unstemmed | Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells |
| title_short | Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells |
| title_sort | conserved mir 370 3p bmp 7 axis regulates the phenotypic change of human vascular smooth muscle cells |
| url | https://doi.org/10.1038/s41598-022-26711-z |
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