Conclusions
We have identified miR-199a-5p as one of the mechanisms employed by hUC-MSCs to alleviate lupus disease associated pathologies in MRL/lpr mice, which is attributable for promoting splenic CD4+ T cell senescence through Sirt1/p53 pathway.
Methods
The effects of hUC-MSCs on lupus syndrome and senescence pathways in MRL/lpr mice in vivo and in vitro were determined. The functional roles of miR-199a-5p in splenic CD4+ T cell senescence were studied by miRNA mimic or inhibitor in vitro. MRL/lpr mice were injected with miR-199a-5p agomir to evaluate the effects of miR-199a-5p on splenic CD4+ T cell senescence and disease in vivo.
Results
We showed that hUC-MSCs transplantation ameliorated lupus symptoms and increased senescence of splenic CD4+ T cells through Sirt1/p53 signaling via miR-199a-5p in MRL/lpr mice. Moreover, systemic delivery of miR-199a-5p in MRL/lpr mice increased splenic CD4+ T-cell senescence, mimicking the therapeutic effects of transplanted hUC-MSCs. Conclusions: We have identified miR-199a-5p as one of the mechanisms employed by hUC-MSCs to alleviate lupus disease associated pathologies in MRL/lpr mice, which is attributable for promoting splenic CD4+ T cell senescence through Sirt1/p53 pathway.