Prevention of infarct scar thinning and dilatation and stimulation of scar contracture can prevent progressive heart failure. Since microRNA 145 (miR‐145) plays an important role in cardiac fibroblast response to wound healing and cardiac repair after an myocardial infarction (MI), using a miR‐145 knock‐out (KO) mouse model, we evaluated contribution of down‐regulation of miR‐145 to cardiac fibroblast and myofibroblast function during adverse cardiac remodelling. Cardiac function decreased more and the infarct size was larger in miR‐145 KO than that in WT mice after MI and this phenomenon was accompanied by a decrease in cardiac fibroblast‐to‐myofibroblast differentiation. Quantification of collagen I and α‐SMA protein levels as well as wound contraction revealed that transdifferentiation of cardiac fibroblasts into myofibroblasts was lower in KO than WT mice. In vitro restoration of miR‐145 induced more differentiation of fibroblasts to myofibroblasts and this effect involved the target genes Klf4 and myocardin. MiR‐145 contributes to infarct scar contraction in the heart and the absence of miR‐145 contributes to dysfunction of cardiac fibroblast, resulting in greater infarct thinning and dilatation. Augmentation of miR‐145 could be an attractive target to prevent adverse cardiac remodelling after MI by enhancing the phenotypic switch of cardiac fibroblasts to myofibroblasts.

中文翻译：

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敲除 MicroRNA 145 会损害心肌成纤维细胞功能和心肌梗塞后的伤口愈合。

预防梗塞疤痕变薄和扩张以及刺激疤痕挛缩可以预防进行性心力衰竭。由于 microRNA 145 (miR-145) 在心肌梗死 (MI) 后心脏成纤维细胞对伤口愈合和心脏修复的反应中起重要作用，因此我们使用 miR-145 敲除 (KO) 小鼠模型评估了miR-145在不良心脏重构过程中对心脏成纤维细胞和肌成纤维细胞功能的调节。与心肌梗死后 WT 小鼠相比，miR-145 KO 的心脏功能下降更多，梗死面积更大，这种现象伴随着心脏成纤维细胞向肌成纤维细胞分化的减少。胶原蛋白 I 和 α-SMA 蛋白水平以及伤口收缩的定量表明，KO 小鼠中心脏成纤维细胞向肌成纤维细胞的转分化低于 WT 小鼠。miR-145 的体外修复诱导成纤维细胞更多地分化为肌成纤维细胞，这种作用涉及靶基因 Klf4 和心肌素。MiR-145 有助于心脏梗塞瘢痕收缩，而 miR-145 的缺失导致心脏成纤维细胞功能障碍，导致梗塞更薄和扩张。通过增强心脏成纤维细胞向肌成纤维细胞的表型转换，miR-145 的增强可能是预防 MI 后不良心脏重构的一个有吸引力的目标。miR-145 的体外修复诱导成纤维细胞更多地分化为肌成纤维细胞，这种作用涉及靶基因 Klf4 和心肌素。MiR-145 有助于心脏梗塞瘢痕收缩，而 miR-145 的缺失导致心脏成纤维细胞功能障碍，导致梗塞更薄和扩张。通过增强心脏成纤维细胞向肌成纤维细胞的表型转换，miR-145 的增强可能是预防 MI 后不良心脏重构的一个有吸引力的目标。miR-145 的体外修复诱导成纤维细胞更多地分化为肌成纤维细胞，这种作用涉及靶基因 Klf4 和心肌素。MiR-145 有助于心脏梗塞瘢痕收缩，而 miR-145 的缺失导致心脏成纤维细胞功能障碍，导致梗塞更薄和扩张。通过增强心脏成纤维细胞向肌成纤维细胞的表型转换，miR-145 的增强可能是预防 MI 后不良心脏重构的一个有吸引力的目标。