MiR-139-5p regulates the Notch/RBP-J/Hes1 axis to promote homing of bone mesenchymal stem cells in bronchial asthma
Objective To observe the role of miR-139-5p and Notch1 signaling pathway in regulation of homing of bone mesenchymal stem cells(BMSCs)of asthmatic rats.Methods Normal rat BMSCs were co-cultured with bronchial epithelial cells from normal or asthmatic rats,followed by transfection with miR-139-5p mimics or a negative control sequence.The changes in cell viability and cell cycle were analyzed,and the cellular expressions of CXCR4 and SDF-1 were detected using immunofluorescence staining.The changes of BMSC homing after the transfection were observed,and the expressions of Notch1,RBP-J,and Hes1 mRNAs and proteins and Th1/Th2 cytokines were detected with RT-qPCR,Western blotting or ELISA.Results The co-cultures of BMSCs and asthmatic bronchial epithelial cells showed significantly decreased expressions of miR-139-5p,IL-2 and IL-12 and increased expressions of CXCR4,SDF-1,IL-5,IL-9,Notch1,RBP-J,and Hes1.Transfection with miR-139-5p mimics significantly increased the expressions of miR-139-5p,IL-2,CXCR4 and SDF-1 and lowered the expression levels of IL-5,IL-9,Notch1,activated Notch1,and Hes1 in the co-cultured cells.Correlation analysis showed that BMSC homing was positively correlated with miR-139-5p and IL-12 and negatively correlated with IL-5 expression.The expression of CXCR4 was negatively correlated with activated Notch1,and SDF-1 was positively correlated with miR-139-5p but negatively correlated with Notch1 expression.Conclusion High expression of miR-139-5p promotes homing of BMSCs in asthma by targeting the Notch1 signaling pathway to regulate the expressions of Th1/Th2 cytokines,thereby alleviating airway inflammation.
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