Objective To investigate the mechanisms of hypoxia-induced cell proliferation of rheumatoid arthritis fibroblast-like synoviocytes(RA-FLS).Methods FLS proliferation in the synovium tissues from patients with RA and osteoarthritis(OA)was detected by hematoxylin-eosin(HE)staining.Primary RA-FLSs were isolated and identified by flow cytometry.RA-FLS was cultured under normoxia(21％O2)or hypoxia(3％O2)condition,and CCK-8 assay was used to detect cell proliferation.The expression of miR-let-7d in FLS was detected with RT-PCR.The miR-let-7d mimic and inhibitor were transfected to RA-FLS,respectively.The role of HMGA2 gene in hypoxia-induced proliferation of RA-FLS was also investigated.Results Compared in OA synovium,the proliferation of FLS in RA synovium was increased significantly.Increased proliferation and down-regulation of miR-let-7d expression was found in RA-FLS under hypoxic environments.Overexpression of miR-let-7d inhibited RA-FLS proliferation,but had no effect in the apoptosis of RA-FLS.Further study indicated that,HMGA2 was a target gene of miR-let-7d in RA-FLS,and was found to be involved in hypoxia-induced proliferation of RA-FLS.Conclusion The miR-let-7d-HMGA2 signaling pathway may be involved in the proliferation of RA-FLS under hypoxia condition.
维普
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