Delivery of let-7i to mice significantly inhibited angiotensin II-induced cardiac inflammation and fibrosis in a dose-dependent manner by suppressing interleukin-6 and multiple collagens.
Does let-7i delivery reduce angiotensin II-induced cardiac inflammation and fibrosis in mouse models?
Let-7i acts as a novel negative regulator of angiotensin II-induced cardiac inflammation and fibrosis, representing a potential therapeutic target.
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.
Wang et al. (Tue,) conducted a other in Angiotensin II-induced cardiac remodeling. let-7i delivery/overexpression vs. let-7i knockdown or control was evaluated on Cardiac inflammation and fibrosis (expression of interleukin-6 and collagens). Delivery of let-7i to mice significantly inhibited angiotensin II-induced cardiac inflammation and fibrosis in a dose-dependent manner by suppressing interleukin-6 and multiple collagens.