ObjectiveTo analyze the core genes associated with rheumatoid arthritis (RA) in fibroblast-like synoviocytes (FLSs) by employing RNA sequencing technique. Methods(1) Thirty SD rats were randomly divided into model group or normal group, with 15 rats in each group. Rats in the model group received injection of complete Freund′s adjuvant to establish the rat model of adjuvant arthritis (classic RA model), and rats in the normal group received injection of sterile normal saline with equivalent volume. The histomorphological changes and cartilage tissue destruction of rats′ knee joint in the two groups were observed by the HE staining and saffron O-fast green staining, respectively. (2) Synovial tissues of rats in the two groups were obtained for FLSs isolation and culture. After analyzing the gene expressions of FLSs in the two groups by the RNA sequencing technique, the R software was used to screen the differentially expressed genes in FLSs of the two groups. The Gene Ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and Gene Set Enrichment Analysis were performed on differentially expressed genes. The protein-protein interaction (PPI) network of differentially expressed genes was constructed and core genes were screened by using the STRING database and Cytoscape software. The real-time fluorescent quantitative PCR was used to validate some differentially expressed genes. ResultsThe results of the HE staining and saffron O-fast green staining revealed that the modeling was successful. A total of 227 differentially expressed genes were screened out, including 133 up-regulated genes and 94 down-regulated genes. Differentially expressed genes were mainly concentrated in biological processes such as negative regulation of smooth muscle cell proliferation, etc.,in cellular compsitions such as lipid particles, etc.,in molecular functions such as calcium ion binding, etc., and in signaling pathways such as regulation of lipolysis in adipocytes, etc. The gene sets enriched by differentially expressed genes were mainly involved in defense response, G protein-coupled receptor signaling pathway, and active molecular transducer. A total of 10 core genes were screened out, including MMP9, AGT, CECR2, FGR, Hist1h3c, APOB, CDH3, MMP15, Hist2h4, and NPPB. The results of the real-time fluorescent quantitative PCR indicated that the mRNA expressions of MMP9, FGR, and APOB in synovial tissues of rats in the model group were higher than those in the normal group (P＜0.05), which was consistent with the RNA sequencing results. ConclusionCore genes such as MMP9, FGR, APOB, etc.,probably participate in the occurrence and development of RA by participating in the regulation of immune inflammatory response.

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