Myocardial fibrosis, a common feature of heart disease, remains an unsolved clinical challenge. Fibrosis resolution requires activation of cardiac fibroblasts exhibiting context-dependent beneficial and detrimental dichotomy. Here, we explored the hypothesis of fibroblast reversible transition between quiescence and activated myofibroblastic states as a manifestation of cell phenotypic switching in myocardial remodelling. In support, gene regulatory networks executing conversion of cardiac fibroblasts to myofibroblasts and vice versa in fibrosis resolution are reconstructed using TRANSPATH database. In a scenario of fibroblast activation triggered by transforming growth factor β, a cardinal mediator of tissue fibrosis, signalling cascades governing entry into or exit from specific fibroblast statures in cardiac fibrotic remodelling were dissected. It is suggested that fibroblast phenotypic switching constitutes the central gait toward guiding cell state-gating strategies to counteract adverse cardiac fibrosis, a devastating disorder with no approved therapeutic option.

中文翻译：

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在心脏重塑中靶向成纤维细胞表型转换是一种很有前途的抗纤维化策略


心肌纤维化是心脏病的常见特征，仍然是一个未解决的临床挑战。纤维化消退需要激活心脏成纤维细胞，表现出上下文依赖性的有益和有害二分法。在这里，我们探讨了成纤维细胞在静止和活化肌成纤维细胞状态之间的可逆转变作为心肌重塑中细胞表型转换的表现的假设。作为支持，使用 TRANSPATH 数据库重建执行心脏成纤维细胞向肌成纤维细胞转化的基因调控网络，反之亦然，在纤维化分辨率中执行转换。在由组织纤维化的主要介质转化生长因子 β 触发的成纤维细胞激活的情况下，解剖了控制心脏纤维化重塑中特定成纤维细胞身材进入或退出的信号级联反应。据表明，成纤维细胞表型转换构成了指导细胞状态门控策略以抵消不良心脏纤维化的中心步态，这是一种没有批准治疗方案的破坏性疾病。