Imatinib inhibits CSF1R that stimulates proliferation of rheumatoid arthritis fibroblast-like synoviocytes.

In this study, we aimed to explore the effects of imatinib on the proliferation of rheumatoid arthritis synovial cell (RA-FLS) and inflammatory responses by regulating CSF1R. Differential genes were screened via microarray analysis, followed by being analysed through the weighted co-expression network (WGCNA) network, that included module and cluster analysis. The relationship between imatinib and genes was visualized using the Search Tool for the Retrieval of Interacting Genes (STITCH) database. Expressions of mRNA and protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. Cell viability was examined via clone formation assay, while cell cycle and apoptosis were analysed through flow cytometry analysis. The hub gene CSF1R was ultimately determined by microarray analysis and WGCNA analysis. Colony-stimulating-factor receptor-1 (SF1R) was highly expressed in rheumatoid arthritis tissues and cells, and CSF1R over-expression could promote inflammatory responses. Moreover, CSF1R could promote RA-FLS proliferation, inhibit apoptosis and accelerate the cell cycle. The targeting relationship between imatinib and CSF1R was also validated in this study. Imatinib attenuated RA-FLS inflammation in a concentration-dependent manner. Meanwhile, imatinib could inhibit RA-FLS proliferation and promote apoptosis, ultimately reducing the damage of RA-FLS. Over-expression of CSF1R accelerated the cell cycle and proliferation of RA-FLS, while inhibiting cell apoptosis. Conversely, imatinib could significantly restrain the cell cycle and viability of RA-FLS and accelerated apoptosis via suppression of CSF1R expression. Further, histological and serological assay investigated and proved the proinflammatory effects of CSF1R in RA rabbits.