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.

心力衰竭主要是由心脏的收缩功能下降引起的。长链非编码 RNA 与心脏病有关。本研究旨在探讨长链非编码 RNAs 睾丸发育相关基因 1 (TDRG1) 对转化生长因子-β1 (TGF-β1) 刺激的人心脏成纤维细胞 (HCFs) 纤维化和炎症反应的影响。通过酶联免疫吸附测定评估促炎细胞因子的水平。应用逆转录定量聚合酶链反应揭示TDRG1、miR-605-3p和肿瘤坏死因子受体超家族（TNFRSF21）的表达水平。制备蛋白质印迹分析以检测TNFRSF21的蛋白质水平和纤维化相关基因。进行荧光素酶报告基因测定以确认 miR-605-3p 和 TDRG1/ TNFRSF21之间的相互作用。我们发现 TGF-β1 刺激的 HCF 显示出高浓度的促炎细胞因子和纤维化相关基因的蛋白质水平增加，表明 TGF-β1 刺激的 HCF 功能障碍。此外，TDRG1 在 TGF-β1 刺激的 HCF 中上调。我们发现干扰 TDRG1 可减轻 TGF-β1 刺激的 HCF 的功能障碍。此外，TDRG1 与 miR-605-3p 结合。MiR-605-3p 在 TGF-β1 处理的 HCF 中发挥抗纤维化和抗炎作用。作为miR-605-3p的靶基因，TNFRSF21逆转了 TDRG1 敲低在 TGF-β1 处理的 HCF 中的抗纤维化和抗炎作用。总体而言，我们的研究证实，TDRG1 通过 miR-605-3p/ TNFRSF21轴加重 TGF-β1 处理的 HCF 的纤维化和炎症反应。