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. 2020 Nov;235(11):7769-7779.
doi: 10.1002/jcp.29386. Epub 2019 Nov 11.

Inhibition of microRNA-150-5p alleviates cardiac inflammation and fibrosis via targeting Smad7 in high glucose-treated cardiac fibroblasts

Hui Che  1   2 , Yueqiu Wang  1 , Yang Li  1 , Jie Lv  1 , Hui Li  1 , Yining Liu  3 , Ruixue Dong  3 , Yongle Sun  1 , Xiaodan Xu  1 , Jie Zhao  1 , Lihong Wang  1
Affiliations

Inhibition of microRNA-150-5p alleviates cardiac inflammation and fibrosis via targeting Smad7 in high glucose-treated cardiac fibroblasts

Hui Che et al. J Cell Physiol. 2020 Nov.

Abstract

Hyperglycemia-induced cardiac fibrosis is a prominent characteristic of diabetic cardiomyopathy. Changes in proinflammatory cytokines have been shown to lead to cardiac fibrosis in patients with diabetes mellitus. This study aimed to investigate the role of miR-150-5p in mediating cardiac inflammation and fibrosis in cardiac fibroblasts (CFs). Herein, we found that high-glucose (HG) treatment significantly induced cardiac inflammation, as manifested by increased proinflammatory cytokine production (IL-1β) and NF-κB activity in CFs. Moreover, HG markedly aggravated cardiac fibrosis and increased levels of fibrotic markers (CTGF, FN, α-SMA) and extracellular matrix proteins (Col-I, Col-III) in CFs. At the same time, HG disturbed the TGF-β1/Smad signaling pathway, as evidenced by increases in TGF-β1 and p-Smad2/3 levels and decreases in Smad7 levels in CFs. Furthermore, we found that miR-150-5p was upregulated by HG, which negatively regulated Smad7 expression at the posttranscription level. Further study demonstrated that cardiac inflammation and fibrosis in CFs were corrected following miR-150-5p knockdown, but exacerbated by miR-150-5p overexpression. These data indicated that miR-150-5p inhibition could ameliorate NF-κB-related inflammation and TGF-β1/Smad-induced cardiac fibrosis through targeting Smad7. Thus, miR-150-5p may be a novel promising target for treating diabetic cardiomyopathy.

Keywords: TGF-β1/Smad; diabetic cardiomyopath; fibrosis; inflammation; microRNA-150-5p.

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References

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