Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 235, Issue 11, Pages 7769-7779Publisher
WILEY
DOI: 10.1002/jcp.29386
Keywords
diabetic cardiomyopath; fibrosis; inflammation; microRNA-150-5p; TGF-beta 1; Smad
Categories
Funding
- China Postdoctoral Science Foundation [2017M621308]
- Natural Science Foundation of Heilongjiang Province [QC2017108]
- National Nature Science Foundation of China [81600935, 81770809]
Ask authors/readers for more resources
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-1 beta) and NF-kappa B activity in CFs. Moreover, HG markedly aggravated cardiac fibrosis and increased levels of fibrotic markers (CTGF, FN, alpha-SMA) and extracellular matrix proteins (Col-I, Col-III) in CFs. At the same time, HG disturbed the TGF-beta 1/Smad signaling pathway, as evidenced by increases in TGF-beta 1 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-kappa B-related inflammation and TGF-beta 1/Smad-induced cardiac fibrosis through targeting Smad7. Thus, miR-150-5p may be a novel promising target for treating diabetic cardiomyopathy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available