Immunomodulatory effect of miR⁃125b⁃5p modified umbilical cord mesenchymal stem cells mediated JAK2/STAT3 signaling pathway on systemic lupus erythematosus / 安徽医科大学学报

ABSTRACT

Objective @#To investigate the imunomodulatory effects of umbilical cord mesenchymal stem cells(UC⁃MSCs) modified by miR⁃125b⁃5p through JAK2/STAT3 pathway on systemic lupus erythematosus(SLE) . @*Methods@#UC⁃MSCs were isolated and cultured under aseptic conditions ; Peripheral blood mononuclear cells ( PBMCs)were separated from SLE patients by density gradient centrifugation. The relative expressions of IL⁃17A , Foxp3 ,IFN⁃γ , IL⁃4 genes in PBMCs cultured with UC⁃MSCs for 48 h were detected by RT⁃qPCR; The relative expressions of JAK2 , p ⁃JAK2 , STAT3 , p ⁃STAT3 and IL⁃18 proteins in kidney tissues of MRL/lpr mice were detected by west⁃ern blot. @*Results @#Compared with the PBMCs culture group , the expression of IFN⁃γ and IL⁃17A and the propor⁃tion of Th17/Treg cells were significantly down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group , UC⁃MSCs + miR⁃NC group and UC⁃MSCs group(P < 0. 01) , the expression of the proportion of Th1/Th2 cells (P < 0. 05) was down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group and UC⁃MSCs + miR⁃NC group ; Compared with the untreated group of MRL/lpr mice , the relative expressions of JAK2 , p ⁃JAK2 , STAT3 , p ⁃STAT3 and IL⁃18 proteins in kidney tissues of MRL/lpr mice were significantly down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group (P < 0. 01) , and the rela⁃tive expressions of IL⁃18 proteins was significantly down⁃regulated in UC⁃MSCs + miR⁃NC group and UC⁃MSCs group (P < 0. 01) .@*Conclusion@#miR⁃125b⁃5p plays a synergistic role in UC⁃MSCs ,which regulates the differenti⁃ation of Th2 cells in PBMCs of SLE patients and the relative expressions of p ⁃JAK2/JAK2 , p ⁃STAT3/STAT3 , and IL⁃18 proteins in kidney tissues of MRL/lpr mice. UC⁃MSCs modified by miR⁃125b⁃5p may play immunomodulato⁃ry effect on SLE by JAK2/STAT3 signaling pathway.