[miR-139 promotes homing of bone marrow mesenchymal stem cells (BMSCs) to lung tissues of asthmatic rats to inhibit inflammatory response of Th2 cells by down-regulating Notch1/Hes1 pathway]

Abstract

Objective To study the effects of microRNA-139 (miR-139) regulating Notch signaling pathway on bone mesenchymal stem cells (BMSCs) homing and asthma airway inflammation. Methods Twenty-four SD rats were randomly divided into normal control group, model control group and BMSCs group. The rats were challenged with ovalbumin and then BMSCs were transplanted into the rats. Pathological changes in lung tissues were observed by HE staining. The expression of BMSCs marker C-X-C motif chemokine receptor 4 (CXCR4) in the lung tissues was examined by flow cytometry, and the expression of CXCR4 in bronchial epithelial cells was observed by immunofluorescence staining. The expression of interferon-γ (IFN-γ) and interleukins-4 (IL-4) were detected by ELISA, and the expression of Notch1, Jagged1 and Hes1 in the lung tissues were tested by Western blot analysis. Results Compared with the normal control group, the expression of CXCR4, IL-4, Notch1 and Hes1 in the lung tissues of the model control group increased significantly, and the ratio of Th1/Th2 cells and the level of miR-139 mRNA decreased. Compared with the model control group, the expression of CXCR4 in the lung tissues and bronchial epithelial cells increased, so were the ratio of Th1/Th2 cells and the level of miR-139 mRNA, while the expression of Notch1 and Hes1 decreased. Correlation analysis showed that the expression of CXCR4 in the lung tissues was positively correlated with the expression of CXCR4 in bronchial epithelial cells, the ratio of Th1/Th2 cells, and miR-139. The expression of CXCR4 in bronchial epithelial cells was positively correlated with the ratio of Th1/Th2 cells, the expression of miR-139, and negatively correlated with the expression of Notch1. The ratio of Th1/Th2 cells was positively correlated with the expression of miR-139. Conclusion miR-139 can down-regulate the Notch pathway and promote BMSCs homing in asthmatic lung tissues, thus suppressing the inflammatory response of Th2 cells through immune regulation.