MBNL1 drives dynamic transitions between fibroblasts and myofibroblasts in cardiac wound healing.
MBNL1 drives dynamic transitions between fibroblasts and myofibroblasts in cardiac wound healing.
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DOI：
10.1016/j.stem.2022.01.012
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发表时间：
2022-03-03
期刊：
影响因子：
23.9
通讯作者：
Davis J
中科院分区：
文献类型：
--
作者：
Bugg D;Bailey LRJ;Bretherton RC;Beach KE;Reichardt IM;Robeson KZ;Reese AC;Gunaje J;Flint G;DeForest CA;Stempien-Otero A;Davis J
动态成纤维细胞到肌成纤维细胞状态的转变是心脏纤维化反应的基础。由于肌盲样1 （MBNL1）的转录组成熟促进了细胞分化状态，本研究调查了战术控制MBNL1活性是否会改变肌成纤维细胞活性和纤维化结果。在健康小鼠心脏成纤维细胞特异性MBNL1的过表达将成纤维细胞转录组转化为肌成纤维细胞转录组，并在损伤后促进肌细胞重塑和疤痕成熟。成纤维细胞和肌成纤维细胞特异性MBNL1的缺失限制了疤痕的产生和稳定，这可归因于可忽略的肌成纤维细胞活性。MBNL1缺失与损伤的结合使静止的成纤维细胞扩大并具有心脏间充质干细胞的特征；然而，转基因MBNL1的表达阻断了成纤维细胞的增殖，使群体进入成熟的肌成纤维细胞状态。这些数据表明MBNL1是一个转录后开关，在心脏伤口愈合过程中控制成纤维细胞状态的可塑性。Bugg和他的同事证明，心肌梗死后MBNL1的表达调节心肌成纤维细胞增殖，但也过渡到和维持活化的肌成纤维细胞状态，这与纤维化瘢痕和心肌重塑的产生和成熟的改变有关。
Dynamic fibroblast to myofibroblast state transitions underlie the heart’s fibrotic response. Because transcriptome maturation by Muscleblind-like 1 (MBNL1) promotes differentiated cell states, this study investigated whether tactical control of MBNL1 activity could alter myofibroblast activity and fibrotic outcomes. In healthy mice cardiac fibroblast-specific overexpression of MBNL1 transitioned the fibroblast transcriptome to that of a myofibroblast and after injury promoted myocyte remodeling and scar maturation. Both fibroblast and myofibroblast-specific loss of MBNL1 limited scar production and stabilization, which was ascribed to negligible myofibroblast activity. The combination of MBNL1 deletion and injury caused quiescent fibroblasts to expand and adopt features of cardiac mesenchymal stem cells; whereas, transgenic MBNL1 expression blocked fibroblast proliferation and drove the population into a mature myofibroblast state. These data suggest MBNL1 is a post-transcriptional switch controlling fibroblast state plasticity during cardiac wound healing. Bugg and colleagues demonstrate that following myocardial infarction MBNL1 expression regulates cardiac fibroblast proliferation but also the transition to and maintenance of an activated myofibroblast state, which was associated with altered production and maturation of fibrotic scaring and cardiac muscle remodeling.
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影响因子：
20.1
作者：
Dobaczewski M;Bujak M;Li N;Gonzalez-Quesada C;Mendoza LH;Wang XF;Frangogiannis NG
通讯作者：
Frangogiannis NG
DOI：
10.1093/bioinformatics/btaa1009
发表时间：
2021-04-05
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Ahlmann-Eltze C;Huber W
通讯作者：
Huber W
影响因子：
16
作者：
Batra, Ranjan;Charizanis, Konstantinos;Manchanda, Mini;Mohan, Apoorva;Li, Moyi;Finn, Dustin J.;Goodwin, Marianne;Zhang, Chaolin;Sobczak, Krzysztof;Thornton, Charles A.;Swanson, Maurice S.
通讯作者：
Swanson, Maurice S.
影响因子：
1.5
作者：
Acharya, Asha;Baek, Seung Tae;Banfi, Serena;Eskiocak, Banu;Tallquist, Michelle D.
通讯作者：
Tallquist, Michelle D.
影响因子：
6.9
作者：
Daseke, Michael J., II;Tenkorang, Mavis A. A.;Lindsey, Merry L.
通讯作者：
Lindsey, Merry L.