Ubiquitin D promotes the progression of rheumatoid arthritis via activation of the p38 MAPK pathway

Ubiquitin D (UBD), a member of the ubiquitin-like modifier family, has been reported to be highly expressed in various types of cancer and its overexpression is positively associated with tumor progression. However, the role and mechanism of UBD in rheumatoid arthritis (RA) remain elusive. In the present study, the gene expression profiles of GSE55457 were downloaded from the Gene Expression Omnibus database to assess differentially expressed genes and perform functional enrichment analyses. UBD was overexpressed by lentivirus transfection. The protein level of UBD, p-p38 and p38 in RA-fibroblast-like synoviocytes (FLSs) were examined by western blotting. Cell Counting Kit-8 and flow cytometry assays were used to detect the functional changes of RA-FLSs transfected with UBD and MAPK inhibitor SB202190. The concentrations of inflammatory factors (IL-2, IL-6, IL-10 and TNF-alpha) were evaluated using ELISA kits. The results revealed that UBD was overexpressed in RA tissues compared with in the healthy control tissues. Functionally, UBD significantly accelerated the viability and proliferation of RA-FLSs, whereas it inhibited their apoptosis. Furthermore, UBD significantly promoted the secretion of inflammatory factors (IL-2, IL-6, IL-10 and TNF-alpha). Mechanistically, elevated UBD activated phospohorylated-p38 in RA-FLSs. By contrast, UBD overexpression and treatment with the p38 MAPK inhibitor SB202190 not only partially relieved the UBD-dependent effects on cell viability and proliferation, but also reversed its inhibitory effects on cell apoptosis. Furthermore, SB202190 partially inhibited the effects of UBD overexpression on the enhanced secretion of inflammatory factors. The present study indicated that UBD may mediate the activation of p38 MAPK, thereby facilitating the proliferation of RA-FLSs and ultimately promoting the progression of RA. Therefore, UBD may be considered a potential therapeutic target and a promising prognostic biomarker for RA.

Automated summary

Ubiquitin D (UBD), highly expressed in rheumatoid arthritis (RA), activates p38 MAPK signaling pathway to promote the proliferation of RA synoviocytes and secretion of inflammatory factors, facilitating the progression of RA. UBD may serve as a potential therapeutic target and prognostic biomarker for RA.