BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP‐1/CEMIP expression
Abstract Background The cardiac repair process following a myocardial infarction is a key factor in patient prognosis. In this repair process, cardiac fibrosis takes a critically important role. Among those featured genes for fibrosis, transforming growth factor beta (TGF‐β) is known to be involved...
| Main Authors: | , , , , , , |
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| Format: | Article |
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Wiley
2023-06-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.1296 |
| _version_ | 1797791850114842624 |
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| author | Guiping Lu Zhuowang Ge Xinyuan Chen Yue Ma Ancai Yuan Yuquan Xie Jun Pu |
| author_facet | Guiping Lu Zhuowang Ge Xinyuan Chen Yue Ma Ancai Yuan Yuquan Xie Jun Pu |
| author_sort | Guiping Lu |
| collection | DOAJ |
| description | Abstract Background The cardiac repair process following a myocardial infarction is a key factor in patient prognosis. In this repair process, cardiac fibrosis takes a critically important role. Among those featured genes for fibrosis, transforming growth factor beta (TGF‐β) is known to be involved in the fibrosis in various organs. And bone morphogenetic protein (BMP)6 belongs to the TGF‐β superfamily. Although BMPs are known to play exclusive roles in cardiac repair processes, the character of BMP6 in cardiac remodelling remains unclear. Purpose This study aimed to investigate how BMP6 functioned in cardiac fibrosis following myocardial infarction (MI). Results In this paper, we demonstrated that BMP6 expression was upregulated after myocardial infarction in wild‐type (WT) mice. Furthermore, BMP6−/− mice showed a more significant decline in cardiac function and lower survival curves after MI. An enlarged infarct area, increased fibrosis and more pronounced inflammatory infiltration were observed in BMP6−/− mice compared to WT mice. The expression of collagen I, collagen III and α‐SMA was increased in BMP6−/− mice. In vitro, through gain‐of‐function and loss‐of‐function experiments, it was demonstrated that BMP6 decreases collagen secretion in fibroblasts. Mechanistically, knocking down BMP6 promoted AP‐1 phosphorylation, which in turn promotes CEMIP expression, led to an acceleration in the progression of cardiac fibrosis. Finally, it was found that rhBMP6 would alleviate ventricular remodelling abnormalities after myocardial infarction. Conclusion Therefore, BMP6 may be a novel molecular target for improving myocardial fibrosis and cardiac function after myocardial infarction. |
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| format | Article |
| id | doaj.art-03f979bffe5545c1800723805306ba1a |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-03-13T02:24:40Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
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| series | Clinical and Translational Medicine |
| spelling | doaj.art-03f979bffe5545c1800723805306ba1a2023-06-30T05:10:38ZengWileyClinical and Translational Medicine2001-13262023-06-01136n/an/a10.1002/ctm2.1296BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP‐1/CEMIP expressionGuiping Lu0Zhuowang Ge1Xinyuan Chen2Yue Ma3Ancai Yuan4Yuquan Xie5Jun Pu6Department of Cardiology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Cardiology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Cardiology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Cardiology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Cardiology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Cardiology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Cardiology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaAbstract Background The cardiac repair process following a myocardial infarction is a key factor in patient prognosis. In this repair process, cardiac fibrosis takes a critically important role. Among those featured genes for fibrosis, transforming growth factor beta (TGF‐β) is known to be involved in the fibrosis in various organs. And bone morphogenetic protein (BMP)6 belongs to the TGF‐β superfamily. Although BMPs are known to play exclusive roles in cardiac repair processes, the character of BMP6 in cardiac remodelling remains unclear. Purpose This study aimed to investigate how BMP6 functioned in cardiac fibrosis following myocardial infarction (MI). Results In this paper, we demonstrated that BMP6 expression was upregulated after myocardial infarction in wild‐type (WT) mice. Furthermore, BMP6−/− mice showed a more significant decline in cardiac function and lower survival curves after MI. An enlarged infarct area, increased fibrosis and more pronounced inflammatory infiltration were observed in BMP6−/− mice compared to WT mice. The expression of collagen I, collagen III and α‐SMA was increased in BMP6−/− mice. In vitro, through gain‐of‐function and loss‐of‐function experiments, it was demonstrated that BMP6 decreases collagen secretion in fibroblasts. Mechanistically, knocking down BMP6 promoted AP‐1 phosphorylation, which in turn promotes CEMIP expression, led to an acceleration in the progression of cardiac fibrosis. Finally, it was found that rhBMP6 would alleviate ventricular remodelling abnormalities after myocardial infarction. Conclusion Therefore, BMP6 may be a novel molecular target for improving myocardial fibrosis and cardiac function after myocardial infarction.https://doi.org/10.1002/ctm2.1296bone morphogenetic protein 6cardiac fibrosismyocardial infarction |
| spellingShingle | Guiping Lu Zhuowang Ge Xinyuan Chen Yue Ma Ancai Yuan Yuquan Xie Jun Pu BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP‐1/CEMIP expression Clinical and Translational Medicine bone morphogenetic protein 6 cardiac fibrosis myocardial infarction |
| title | BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP‐1/CEMIP expression |
| title_full | BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP‐1/CEMIP expression |
| title_fullStr | BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP‐1/CEMIP expression |
| title_full_unstemmed | BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP‐1/CEMIP expression |
| title_short | BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP‐1/CEMIP expression |
| title_sort | bmp6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating ap 1 cemip expression |
| topic | bone morphogenetic protein 6 cardiac fibrosis myocardial infarction |
| url | https://doi.org/10.1002/ctm2.1296 |
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