Long Noncoding RNAs Testis Development Related Gene 1 Aggravates Transforming Growth Factor-β1-Induced Fibrogenesis and Inflammatory Response of Cardiac Fibroblasts Via miR-605-3p/Tumor Necrosis Factor Receptor Superfamily-21 Axis.

Jinghua Cheng, Yi Tang, Xiaomin Cai, Jianbin Gong

Journal of cardiovascular pharmacology 2022 Mar 01

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Heart failure is mainly caused by a decline in the systolic function of the heart. Long noncoding RNAs are related to cardiac diseases. This study aimed to explore the effects of long noncoding RNAs testis development related gene 1 (TDRG1) on the fibrogenesis and inflammatory response of transforming growth factor-beta1 (TGF-β1)-stimulated human cardiac fibroblasts (HCFs). Levels of proinflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Reverse-transcription quantitative polymerase chain reaction was applied to reveal the expression levels of TDRG1, miR-605-3p, and tumor necrosis factor receptor superfamily (TNFRSF21). Western blot analysis was prepared to detect protein levels of TNFRSF21 and fibrosis-related genes. Luciferase reporter assay was conducted for confirming the interaction between miR-605-3p and TDRG1/TNFRSF21. We found that TGF-β1-stimulated HCFs showed high concentrations of proinflammatory cytokines and increased protein levels of fibrosis-related genes, suggesting the dysfunctions of TGF-β1-stimulated HCFs. In addition, TDRG1 was upregulated in TGF-β1-stimulated HCFs. We found that interfering with TDRG1 alleviated dysfunctions of TGF-β1-stimulated HCFs. Moreover, TDRG1 bound with miR-605-3p. MiR-605-3p exerted the antifibrogenic and anti-inflammatory effects in TGF-β1-treated HCFs. As a target gene of miR-605-3p, TNFRSF21 reversed the antifibrogenic and anti-inflammatory effects of TDRG1 knockdown in TGF-β1-treated HCFs. Overall, our study confirmed that TDRG1 aggravates fibrogenesis and inflammatory response in TGF-β1-treated HCFs via the miR-605-3p/TNFRSF21 axis. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Jinghua Cheng, Yi Tang, Xiaomin Cai, Jianbin Gong. Long Noncoding RNAs Testis Development Related Gene 1 Aggravates Transforming Growth Factor-β1-Induced Fibrogenesis and Inflammatory Response of Cardiac Fibroblasts Via miR-605-3p/Tumor Necrosis Factor Receptor Superfamily-21 Axis. Journal of cardiovascular pharmacology. 2022 Mar 01;79(3):296-303