Open AccessmiR‐21 promotes cardiac fibroblast‐to‐myofibroblast transformation and myocardial fibrosis by targeting Jagged1
Author(s) -
Zhou Xueliang,
Xu Hua,
Liu Zhibo,
Wu Qicai,
Zhu Rongrong,
Liu Jichun
Publication year - 2018
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.13654
Subject(s) - myofibroblast , cardiac fibrosis , myocardial fibrosis , gene knockdown , fibroblast , myocardial infarction , fibrosis , cardiac function curve , cancer research , ligation , medicine , chemistry , biology , pathology , in vitro , apoptosis , heart failure , biochemistry
Myocardial fibrosis after myocardial infarction ( MI ) is a leading cause of heart diseases. MI activates cardiac fibroblasts ( CF s) and promotes CF to myofibroblast transformation ( CMT ). This study aimed to investigate the role of miR‐21 in the regulation of CMT and myocardial fibrosis. Primary rat CF s were isolated from young SD rats and treated with TGF ‐β1, miR‐21 sponge or Jagged1 si RNA . Cell proliferation, invasion and adhesion were detected. MI model was established in male SD rats using LAD ligation method and infected with recombinant adenovirus. The heart function and morphology was evaluated by ultrasonic and histological analysis. We found that TGF ‐β1 induced the up‐regulation of miR‐21 and down‐regulation of Jagged1 in rat CF s. Luciferase assay showed that miR‐21 targeted 3′‐ UTR of Jagged1 in rat CF s. miR‐21 sponge inhibited the transformation of rat CF s into myofibroblasts, and abolished the inhibition of Jagged1 mRNA and protein expression by TGF ‐β1. Furthermore, these effects of miR‐21 sponge on rat CFS were reversed by si RNA mediated knockdown of Jagged1. In vivo, heart dysfunction and myocardial fibrosis in MI model rats were partly improved by miR‐21 sponge but were aggravated by Jagged1 knockdown. Taken together, these results suggest that miR‐21 promotes cardiac fibroblast‐to‐myofibroblast transformation and myocardial fibrosis by targeting Jagged1. miR‐21 and Jagged1 are potential therapeutic targets for myocardial fibrosis.