2023, Vol. 27 ›› Issue (10): 1492-1500

Therapeutic effect of umbilical cord mesenchymal stem cells modified by miR-1-5p in MRL/lpr lupus mice

Ding Lili1, Hu Mingzhi1, Wu Zhihui1, Sun Xiaolin2, Wang Yongfu1   

Abstract: BACKGROUND: Numerous studies have shown that mesenchymal stem cells can treat autoimmune diseases through a variety of immunomodulatory pathways, and genetic modification may improve the therapeutic potential of mesenchymal stem cells. MiR-1-5p is lowly expressed in systemic lupus erythematosus, and mesenchymal stem cells overexpressing miR-1-5p may have a therapeutic effect on systemic lupus erythematosus.  
OBJECTIVE: To investigate whether miR-1-5p-modified umbilical cord mesenchymal stem cells mediate the JAK2/STAT3 pathway and have a therapeutic effect on systemic lupus erythematosus MRL/lpr model mice.
METHODS: Twenty MRL/lpr lupus mice were randomly divided into miR-1-5p transfected umbilical cord mesenchymal stem cells treatment group (UC-MSCs+miR-1-5p group), miRNA negative control transfected umbilical cord mesenchymal stem cells treatment group (UC-MSCs+miR-NC group), umbilical cord mesenchymal stem cell treatment group (UC-MSCs group), PBS treatment group (PBS group), and MRL/lpr lupus mice untreated (control group). MRL/lpr lupus mice were treated with tail vein transplantation, once a week, 5 times. Mice were sacrificed at 1-week intervals after the end of treatment. Hematoxylin-eosin staining was used to observe the pathological changes of liver tissue and intestinal tissue of MRL/lpr mice in each group. Western blot assay was used to detect JAK2/STAT3 pathway proteins and their phosphorylation levels and expression levels of interleukin-18 in kidney tissue of mice in each group.  
RESULTS AND CONCLUSION: (1) Compared with control group, the infiltration of inflammatory cells in liver tissue of MRL/lpr mice in UC-MSCs+miR-1-5p group, UC-MSCs+miR-NC group, and UC-MSCs group decreased significantly, and hepatocyte edema and degeneration could be seen in UC-MSCs+miR-NC group. Goblet cells in intestinal tissue of MRL/lpr mice in UC-MSCs+miR-1-5p group increased significantly, but there was no significant difference among other groups. (2) Compared with control group, the expression of p-JAK2 (Y1007+Y1008), p-STAT3 (s727) and interleukin-18 in renal tissue of lupus mice in UC-MSCs+miR-1-5p group was significantly down-regulated (P < 0.05); p-STAT3(s727) (P < 0.05) and interleukin-18 (P < 0.01) were significantly down-regulated in the kidney tissue of lupus mice in UC-MSCs group; expression level of interleukin-18 in UC-MSCs+miR-NC group was significantly down-regulated (P < 0.05); and there was no significant difference in the expression of p-STAT3 (Y705) in renal tissue of lupus mice of each group (P > 0.05). The expression of interleukin-18 in UC-MSCs group was significantly lower than that in PBS group (P < 0.05). (3) The results suggested that umbilical cord mesenchymal stem cells modified by miR-1-5p may alleviate liver and intestinal damage in MRL/lpr mice by inhibiting the activation of JAK2/STAT3 pathway and the expression of interleukin 18, thereby playing a certain therapeutic role in lupus mice.
Key words: miR-1-5p, umbilical cord-mesenchymal stem cell, systemic lupus erythematosus, JAK2/STAT3 signaling pathway, interleukin-18