Kruppel like factor 10 up-regulates PDZ and LIM domain containing protein 2 via nuclear factor kappa-B pathway to inhibit proliferation and inflammatory of fibroblastoid synovial cell in rheumatoid arthritis

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-kappa B 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-kappa B pathway. Overall, KLF10 can up-regulate PDLIM2 by regulating the NF-kappa B pathway to inhibit inflammation and proliferation of HFLSs-RA.

Automated summary

This study reveals the important roles of KLF10 and PDLIM2 in the inflammation and proliferation of RA-FLS. Overexpression of PDLIM2 inhibits the proliferation, migration, and inflammation of RA-FLS, while KLF10 can activate PDLIM2 transcriptionally. The inhibition effects of PDLIM2 overexpression can be reversed by interfering with KLF10, possibly through the NF-κB pathway.