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Research Article

ATF3通过促进RGS1转录调节关节镜检查后滑膜成纤维细胞的增殖、迁移和凋亡

卷 23, 期 9, 2023

发表于: 31 May, 2023

页: [981 - 990] 页: 10

弟呕挨: 10.2174/1566524023666230417084150

价格: $65

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摘要

背景：骨关节炎（OA）是一种涉及软骨和滑膜的退行性关节疾病。据报道，OA 中激活转录因子 3 (ATF3) 和 G 蛋白信号传导调节因子 1 (RGS1) 上调。然而，人们对这两个基因之间的关系以及这种关系在 OA 发展中的机制知之甚少。因此，本研究探讨ATF3介导的RGS1在滑膜成纤维细胞增殖、迁移和凋亡中的机制。 方法：通过TGF-β1诱导构建OA细胞模型后，单独转染ATF3 shRNA或RGS1 shRNA或共转染ATF3 shRNA和pcDNA3.1-RGS1的人成纤维样滑膜细胞（HFLS）。然后，测量增殖、迁移、凋亡以及 ATF3、RGS1、α-SMA、BCL-2、caspase3 和 cleaved-caspase3 的表达。同时，预测并验证了ATF3和RGS1之间的潜在关系。 结果与讨论：GSE185059 数据集的分析表明，RGS1 在 OA 滑液外泌体中上调。此外，ATF3和RGS1在TGF-β1诱导的HFLS中均高表达。 ATF3 shRNA 或 RGS1 shRNA 的转染显着减少了 TGF-β1 诱导的 HFLS 的增殖和迁移，并促进了细胞凋亡。从机制上讲，ATF3 与 RGS1 启动子结合并升高 RGS1 表达。沉默 ATF3 可通过下调 RGS1 抑制 TGF-β1 诱导的 HFLS 的增殖和迁移并增强细胞凋亡。 结论：在TGF-β1诱导的滑膜成纤维细胞中，ATF3与RGS1启动子结合并增强RGS1表达，加速细胞增殖并阻断细胞凋亡。

关键词: 骨关节炎,激活转录因子3,G蛋白信号调节因子1,成纤维细胞,纤维化,增殖,迁移,凋亡。

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