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CircularRNA circ_0071269 knockdown protects against from diabetic cardiomyopathy injury by microRNA-145/gasdermin A axis.

Authors:
Lanfang Fu Juyun Zhang Zhu Lin Yi Li Guijun Qin

Bioengineered 2022 02;13(2):2398-2411

Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.

Circular RNAs (circRNAs) are involved in the development and progression of diabetic cardiomyopathy (DCM). However, the specific function and underlying mechanism of circ_0071269 in DCM remains unclear. In our study, mRNA and miRNA expression was detected by real-time quantitative PCR (qRT-PCR). RNase R and actinomycin D treatment were applied to test the characteristics of circ_0071269. Cell Counting Kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) and enzyme-linked immunosorbent assay (ELISA) kits were performed to determine the cell viability, cell LDH content and interleukin (IL)-1β and IL-18 levels, respectively. Cell death rate was determined by Flow cytometry, and Western blotting was for the protein expression levels. In addition, luciferase reporter and RNA pull-down assays were performed to confirm the binding relationship between miR-145 and circ_0071269 or gasdermin A (GSDMA). Echocardiography, Hematoxylin and Eosin (HE) Staining, and Immunohistochemical (IHC) Staining were performed to evaluate myocardial damage . We found that circ_0071269 was significantly overexpressed in H9c2 cells upon treatment with high glucose. Knockdown of circ_0071269 promoted cell viability and inhibited the inflammatory response, cytotoxicity, and pyroptosis of H9c2 cells . Moreover, circ_0071269 sponges miR-145 to upregulate GSDMA. A miR-145 inhibitor antagonized the effects of circ_0071269 knockdown on the cellular functions of H9c2 cells, while the effects of miR-145 were abrogated by the overexpression of GSDMA. Meanwhile, knockdown of circ_0071269 attenuated cardiac dysfunction of DM mice. Hence, circ_0071269 may promote the development of DCM through the miR-145/GSDMA axis and thus provide a novel marker for the treatment of DCM.

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http://dx.doi.org/10.1080/21655979.2021.2024688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974193PMC
February 2022

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