MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction
MicroRNA (miR: small noncoding RNA)-150 is evolutionarily conserved and is downregulated in patients with diverse forms of heart failure (HF) and in multiple mouse models of HF. Moreover, miR-150 is markedly correlated with the outcome of patients with HF. We previously reported that systemic or car...
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2024-12-01
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| author | Satoshi Kawaguchi Marisa N. Sepúlveda Jian-peng Teoh Taiki Hayasaka Bruno Moukette Tatsuya Aonuma Hyun Cheol Roh Meena S. Madhur Il-man Kim |
| author_facet | Satoshi Kawaguchi Marisa N. Sepúlveda Jian-peng Teoh Taiki Hayasaka Bruno Moukette Tatsuya Aonuma Hyun Cheol Roh Meena S. Madhur Il-man Kim |
| author_sort | Satoshi Kawaguchi |
| collection | DOAJ |
| description | MicroRNA (miR: small noncoding RNA)-150 is evolutionarily conserved and is downregulated in patients with diverse forms of heart failure (HF) and in multiple mouse models of HF. Moreover, miR-150 is markedly correlated with the outcome of patients with HF. We previously reported that systemic or cardiomyocyte-derived miR-150 in mice elicited myocardial protection through the inhibition of cardiomyocyte death, without affecting neovascularization and T cell infiltration. Our mechanistic studies also showed that the protective roles of miR-150 in ischemic mouse hearts and human cardiac fibroblasts were, in part, attributed to the inhibition of fibroblast activation via the repression of multiple profibrotic genes. However, the extent to which miR-150 expression in adult myofibroblasts (MFs) modulates the response to myocardial infarction (MI) remains unknown. Here, we develop a novel 4-hydroxytamoxifen-inducible MF-specific miR-150 conditional knockout mouse model and demonstrate that the mouse line exhibits worse cardiac dysfunction after MI. Our studies further reveal that miR-150 ablation selectively in adult MFs exacerbates cardiac damage and apoptosis after chronic MI. Lastly, MF-specific miR-150 deletion in adult mice promotes the expression of proinflammatory and profibrotic genes as well as cardiac fibrosis following chronic MI. Our findings indicate a key protective role for MF-derived miR-150 in modulating post-MI responses. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-f49e0d0b83054f79ba3ff816f3d433fc2024-12-27T14:14:04ZengMDPI AGBiomolecules2218-273X2024-12-011412165010.3390/biom14121650MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial InfarctionSatoshi Kawaguchi0Marisa N. Sepúlveda1Jian-peng Teoh2Taiki Hayasaka3Bruno Moukette4Tatsuya Aonuma5Hyun Cheol Roh6Meena S. Madhur7Il-man Kim8Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USADivision of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USAMicroRNA (miR: small noncoding RNA)-150 is evolutionarily conserved and is downregulated in patients with diverse forms of heart failure (HF) and in multiple mouse models of HF. Moreover, miR-150 is markedly correlated with the outcome of patients with HF. We previously reported that systemic or cardiomyocyte-derived miR-150 in mice elicited myocardial protection through the inhibition of cardiomyocyte death, without affecting neovascularization and T cell infiltration. Our mechanistic studies also showed that the protective roles of miR-150 in ischemic mouse hearts and human cardiac fibroblasts were, in part, attributed to the inhibition of fibroblast activation via the repression of multiple profibrotic genes. However, the extent to which miR-150 expression in adult myofibroblasts (MFs) modulates the response to myocardial infarction (MI) remains unknown. Here, we develop a novel 4-hydroxytamoxifen-inducible MF-specific miR-150 conditional knockout mouse model and demonstrate that the mouse line exhibits worse cardiac dysfunction after MI. Our studies further reveal that miR-150 ablation selectively in adult MFs exacerbates cardiac damage and apoptosis after chronic MI. Lastly, MF-specific miR-150 deletion in adult mice promotes the expression of proinflammatory and profibrotic genes as well as cardiac fibrosis following chronic MI. Our findings indicate a key protective role for MF-derived miR-150 in modulating post-MI responses.https://www.mdpi.com/2218-273X/14/12/1650cardiac remodelingheart failuremicroRNAsmyocardial infarctionmyofibroblast gene regulationprofibrotic genes |
| spellingShingle | Satoshi Kawaguchi Marisa N. Sepúlveda Jian-peng Teoh Taiki Hayasaka Bruno Moukette Tatsuya Aonuma Hyun Cheol Roh Meena S. Madhur Il-man Kim MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction Biomolecules cardiac remodeling heart failure microRNAs myocardial infarction myofibroblast gene regulation profibrotic genes |
| title | MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction |
| title_full | MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction |
| title_fullStr | MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction |
| title_full_unstemmed | MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction |
| title_short | MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction |
| title_sort | microrna 150 deletion from adult myofibroblasts augments maladaptive cardiac remodeling following chronic myocardial infarction |
| topic | cardiac remodeling heart failure microRNAs myocardial infarction myofibroblast gene regulation profibrotic genes |
| url | https://www.mdpi.com/2218-273X/14/12/1650 |
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