Rheumatology and Immunology Department, the First People's Hospital of Hefei, The Third Affiliated Hospital of Anhui Medical University. Anhui, China.
Bioengineered. 2022 Jan;13(1):1779-1790. doi: 10.1080/21655979.2021.1995992.
Rheumatoid arthritis (RA) is an autoimmune disease caused by synovitis. Two genes, KLF10 (Kruppel like factor 10) and PDZ and LIM domain containing protein 2 (PDLIM2), play key roles in cell inflammation and proliferation. However, the specific roles of the two on inflammation and proliferation of RA-fibroblastoid synovial cell (RA-FLS) have not been reported so far. RT-qPCR and Western blot detected the expressions of PDLIM2 and KLF10 in Human Rheumatoid arthritis FLSs (HFLSs-RA). Cell transfection techniques overexpressed PDLIM2 and KLF10 or inhibited the expression of KLF10. JAPAR database predicted the binding sites of PDLIM2 and KLF10, and the binding between the two was detected and verified using luciferase reporter genes and ChIP. Subsequently, CCK-8 technology, TUNEL staining, Western blot, wound healing and ELISA detected proliferation-related indicators, migration-related indications and inflammation-related indicators. Finally, western blot was used to detect the expression of NF-κB pathway-related proteins to further explore the mechanism.The expression of PDLIM2 was decreased in HFLSs-RA. Overexpression of PDLIM2 inhibited proliferation, migration and inflammation in HFLSs-RA. KLF10 can transcriptionally activate PDLIM2. Interfering with KLF10 reversed the inhibition effects of PDLIM2 overexpression on the proliferation, migration and inflammation, which was possibly through the NF-κB pathway. Overall, KLF10 can up-regulate PDLIM2 by regulating the NF-κB pathway to inhibit inflammation and proliferation of HFLSs-RA.
类风湿关节炎（RA）是一种由滑膜炎引起的自身免疫性疾病。两个基因，Kruppel 样因子 10（KLF10）和 PDZ 和 LIM 结构域蛋白 2（PDLIM2），在细胞炎症和增殖中发挥关键作用。然而，这两个基因在 RA 成纤维样滑膜细胞（RA-FLS）的炎症和增殖中的具体作用尚未有报道。实时定量 PCR 和 Western blot 检测了人类风湿关节炎成纤维样滑膜细胞（HFLSs-RA）中 PDLIM2 和 KLF10 的表达。细胞转染技术过表达 PDLIM2 和 KLF10 或抑制 KLF10 的表达。JAPAR 数据库预测了 PDLIM2 和 KLF10 的结合位点，并通过荧光素酶报告基因和 ChIP 检测和验证了两者之间的结合。随后，CCK-8 技术、TUNEL 染色、Western blot、划痕愈合和 ELISA 检测了增殖相关指标、迁移相关指标和炎症相关指标。最后，Western blot 用于检测 NF-κB 通路相关蛋白的表达，以进一步探讨其机制。在 HFLSs-RA 中，PDLIM2 的表达减少。过表达 PDLIM2 抑制 HFLSs-RA 的增殖、迁移和炎症。KLF10 可以转录激活 PDLIM2。干扰 KLF10 逆转了 PDLIM2 过表达对增殖、迁移和炎症的抑制作用，这可能是通过 NF-κB 通路。总的来说，KLF10 可以通过调节 NF-κB 通路上调 PDLIM2，从而抑制 HFLSs-RA 的炎症和增殖。
