MicroRNA Let-7i Negatively Regulates Cardiac Inflammation and Fibrosis
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.
- Received March 26, 2015.
- Revision received April 8, 2015.
- Accepted June 25, 2015.
- © 2015 The Authors.
Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.