Yanghe Pingchuan granule promotes BMSCs homing in asthmatic rats by upregulating miR-139-5p and downregulating Notch1/Hes1 pathway

Abstract

To observe the effect of Yanghe Pingchuan (YHPC) granule on miR-139-5p, Notch1/Hes1 pathway and homing of bone marrow-derived mesenchymal stem cells (BMSCs) in asthmatic rats. Fifty SD rats were randomized divided into normal control (NC) group, asthmatic model group, BMSCs transplantation group, BMSCs + dexamethasone (0.0625 mg/kg daily) group, and BMSCs+YHPC granule (3.5 g/kg daily) group. In all but the normal control group, asthmatic rat models were established by ovalbumin challenge, and BMSCs (1×106/mL) transplantation via the tail vein was performed in the latter 3 groups on last day of ovalbumin challenge. In all the groups, lung pathologies of the rats were evaluated using HE staining after the treatments. Flow cytometry was employed to detect pulmonary expression of CXCR4 protein, and ELISA was used to determine the expressions of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the lung tissue. The expressions of CXCR4, Notch1 and Hes1 in bronchial epithelial cells was examined using immunofluorescence assay. RT-PCR was used to detect the expressions of miR-139-5p, Notch1, Jagged1, RBP-J and Hes1 mRNAs, and the protein expressions of Notch1, Jagged1 and Hes1 were detected with Western blotting. Compared with the normal control rats, the asthmatic rats exhibited significantly increased expressions of CXCR4, IL-4, Notch1, Jagged1, RBP-J, and Hes1 mRNA and Notch1, Jagged1, and Hes1 proteins and lowered expressions of INF-γ mRNA and miR-139-5p in the lung tissues (P < 0.05 or 0.01). Compared with those in the asthmatic model group, the mRNA expressions of CXCR4, IFN-γ, and miR-139-5p increased and the expressions of IL-4, Notch1, Jagged1, RBP-J, and Hes1 mRNA and Notch1, Jagged1, and Hes1 proteins decreased significantly in the 3 groups with BMSCs transplantation (P < 0.05 or 0.01). The rats in BMSCs+YHPC granule group showed significantly higher CXCR4, IFN-γ, and miR-139-5p mRNA expressions and lower IL-4 and Notch1 mRNA expressions than those in BMSCs transplantation group (P < 0.05). YHPC granule can enhance the inhibitory effect of BMSCs homing on Th2 inflammatory response in asthmatic rats by up-regulating miR-139-5p and down-regulating Notch1/Hes1 pathway.