Open AccessKnock‐out of MicroRNA 145 impairs cardiac fibroblast function and wound healing post‐myocardial infarction
Author(s) -
Song HuiFang,
He Sheng,
Li ShuHong,
Wu Jun,
Yin Wenjuan,
Shao Zhengbo,
Du Guoqing,
Wu Jie,
Li Jiao,
Weisel Richard D.,
Verma Subodh,
Xie Jun,
Li RenKe
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15597
Subject(s) - myofibroblast , wound healing , fibroblast , cardiac function curve , cardiac fibrosis , myocardial infarction , medicine , transdifferentiation , fibrosis , heart failure , cardiology , pathology , microbiology and biotechnology , biology , surgery , stem cell , in vitro , biochemistry
Abstract 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.