Original ArticleLong 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 AxisCheng, Jinghua MD*,†; Tang, Yi MD†; Cai, Xiaomin MD†; Gong, Jianbin MD† Author Information *Third Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; and †Jinling Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. Correspondence: Jianbin Gong, MD, Jinling Clinical Medical College of Nanjing University of Chinese Medicine, 305 East Zhongshan Rd, Nanjing, Jiangsu, China 210002 (e-mail: [email protected]). The authors report no conflicts of interest. Journal of Cardiovascular Pharmacology: March 2022 - Volume 79 - Issue 3 - p 296-303 doi: 10.1097/FJC.0000000000001173 Buy Metrics Abstract 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.