Open AccessMicroRNA Let-7i Negatively Regulates Cardiac Inflammation and Fibrosis
Author(s) -
Xia Wang,
Hongxia Wang,
Yulin Li,
Congcong Zhang,
Chunyu Zhou,
Lei Wang,
Yunlong Xia,
Jie Du,
Huihua Li
Publication year - 2015
Publication title -
hypertension
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.986
H-Index - 265
eISSN - 1524-4563
pISSN - 0194-911X
DOI - 10.1161/hypertensionaha.115.05548
Subject(s) - gene knockdown , angiotensin ii , cardiac fibrosis , inflammation , fibrosis , renin–angiotensin system , microrna , endocrinology , microarray analysis techniques , medicine , gene expression , fibroblast , biology , gene , blood pressure , biochemistry , in vitro
Angiotensin II stimulates fibroblast proliferation and substantially alters gene expression patterns leading to cardiac remodeling, but the mechanisms for such differences are unknown. MicroRNAs are a novel mechanism for gene expression regulation. Herein, we tested the miRNA and mRNA expression patterns in mouse heart using microarray assay and investigated their role in angiotensin II–induced cardiac remodeling. We found that let-7i was dynamically downregulated in angiotensin II–infused heart at day 3 and 7 and had the most targets that were mainly associated with cardiac inflammation and fibrosis. Overexpression or knockdown of let-7i in cultured cardiac fibroblasts demonstrated that let-7i played an inhibitory effect on the expression of its targets interleukin-6 and collagens. Furthermore, delivery of let-7i to mouse significantly inhibited angiotensin II–induced cardiac inflammation and fibrosis in a dose-dependent manner. Conversely, knockdown of let-7i aggravated this effect. Together, our results clearly demonstrate that let-7i acts as a novel negative regulator of angiotensin II–induced cardiac inflammation and fibrosis by suppressing the expression of interleukin-6 and multiple collagens in the heart and may represent a new potential therapeutic target for treating hypertensive cardiac fibrosis.