Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from rupture
Abstract Follistatin‐like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type‐specific regulation of Fstl1 and its function in a murine model of MI. Fstl1 was robustly expressed in fibroblasts and myofibrobla...
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-05-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201506151 |
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| author | Sonomi Maruyama Kazuto Nakamura Kyriakos N Papanicolaou Soichi Sano Ippei Shimizu Yasuhide Asaumi Maurice J van den Hoff Noriyuki Ouchi Fabio A Recchia Kenneth Walsh |
| author_facet | Sonomi Maruyama Kazuto Nakamura Kyriakos N Papanicolaou Soichi Sano Ippei Shimizu Yasuhide Asaumi Maurice J van den Hoff Noriyuki Ouchi Fabio A Recchia Kenneth Walsh |
| author_sort | Sonomi Maruyama |
| collection | DOAJ |
| description | Abstract Follistatin‐like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type‐specific regulation of Fstl1 and its function in a murine model of MI. Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4‐expressing fibroblast lineage cells (Fstl1‐cfKO mice) led to a reduction in injury‐induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase. Cardiac rupture was associated with a diminished number of myofibroblasts and decreased expression of extracellular matrix proteins. The infarcts of Fstl1‐cfKO mice displayed weaker birefringence, indicative of thin and loosely packed collagen. Mechanistically, the migratory and proliferative capabilities of cardiac fibroblasts were attenuated by endogenous Fstl1 ablation. The activation of cardiac fibroblasts by Fstl1 was mediated by ERK1/2 but not Smad2/3 signaling. This study reveals that Fstl1 is essential for the acute repair of the infarcted myocardium and that stimulation of early fibroblast activation is a novel function of Fstl1. |
| format | Article |
| id | doaj-art-2ce0c21a8ef943a1bae844fbcfa3cc6a |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-2ce0c21a8ef943a1bae844fbcfa3cc6a2025-08-20T03:42:52ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-05-018894996610.15252/emmm.201506151Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from ruptureSonomi Maruyama0Kazuto Nakamura1Kyriakos N Papanicolaou2Soichi Sano3Ippei Shimizu4Yasuhide Asaumi5Maurice J van den Hoff6Noriyuki Ouchi7Fabio A Recchia8Kenneth Walsh9Department of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of MedicineDepartment of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of MedicineDepartment of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of MedicineDepartment of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of MedicineDepartment of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of MedicineDepartment of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of MedicineDepartment of Anatomy, Embryology and Physiology, Academic Medical CenterMolecular Cardiovascular Medicine, Nagoya University Graduate School of MedicineCardiovascular Research Center, Lewis Katz School of Medicine at Temple UniversityDepartment of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of MedicineAbstract Follistatin‐like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type‐specific regulation of Fstl1 and its function in a murine model of MI. Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4‐expressing fibroblast lineage cells (Fstl1‐cfKO mice) led to a reduction in injury‐induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase. Cardiac rupture was associated with a diminished number of myofibroblasts and decreased expression of extracellular matrix proteins. The infarcts of Fstl1‐cfKO mice displayed weaker birefringence, indicative of thin and loosely packed collagen. Mechanistically, the migratory and proliferative capabilities of cardiac fibroblasts were attenuated by endogenous Fstl1 ablation. The activation of cardiac fibroblasts by Fstl1 was mediated by ERK1/2 but not Smad2/3 signaling. This study reveals that Fstl1 is essential for the acute repair of the infarcted myocardium and that stimulation of early fibroblast activation is a novel function of Fstl1.https://doi.org/10.15252/emmm.201506151cardiokinefibrosisinfarct healingmyocardial infarction |
| spellingShingle | Sonomi Maruyama Kazuto Nakamura Kyriakos N Papanicolaou Soichi Sano Ippei Shimizu Yasuhide Asaumi Maurice J van den Hoff Noriyuki Ouchi Fabio A Recchia Kenneth Walsh Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from rupture EMBO Molecular Medicine cardiokine fibrosis infarct healing myocardial infarction |
| title | Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from rupture |
| title_full | Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from rupture |
| title_fullStr | Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from rupture |
| title_full_unstemmed | Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from rupture |
| title_short | Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from rupture |
| title_sort | follistatin like 1 promotes cardiac fibroblast activation and protects the heart from rupture |
| topic | cardiokine fibrosis infarct healing myocardial infarction |
| url | https://doi.org/10.15252/emmm.201506151 |
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