Journal of Southern Medical University

Journal of Southern Medical University ›› 2021, Vol. 41 ›› Issue (10): 1464-1472.doi: 10.12122/j.issn.1673-4254.2021.10.04

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Inhibition of the Notch1/Jagged1 pathway promotes homing of bone mesenchymal stem cells to improve asthma in rats

WANG Kun, ZHU Huizhi, YANG Lei, XU Qingwen, REN Fengchun, LIU Xiangguo   

  1. Key Laboratory of Xin'an Medical Education Ministry, Hefei 230031, China; Huixue Research Center (Anhui University of Chinese Medicine Branch), Hefei 230031, China; School of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China; Graduate School, College of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China
  • Online:2021-10-20 Published:2021-11-11

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Abstract: Objective To explore the association of the Notch1/Jagged1 pathway with the homing of mesenchymal stem cells (BMSCs) to regulate Th1/Th2 drift in asthma. Methods Twenty SD rats were randomly divided into normal control group, model group, BMSC transplantation group, and BMSC+Notch inhibitor group. Ovalbumin sensitization was used to establish rat models of asthma, and BMSCs were transplanted via the tail vein. The pathology of the lung tissue was examined with HE staining, and the contents of interleukin (IL)-5, IL-13, and interferon-γ (IFN-γ) in lung tissue homogenate were determined with enzyme-linked immunosorbent assay. The expressions of Notch1 and Jagged1 mRNA were detected with RT-PCR, and CXCR4 expression in the bronchial epithelial cells was examined using immunofluorescence staining; Western blotting was used to detect the protein expressions of T-bet, GATA-3, Notch1, and Jagged1 in the lung tissue. Results Compared with those in the control group, the expressions of IFN-γ and T-bet proteins decreased significantly and the pulmonary expressions of IL-5, IL-13, and GATA-3 proteins as well as Notch1 and Jagged1 mRNA and protein expressions all increased significantly in the model group (P<0.05 or 0.01). Compared with those in the model group, CXCR4, IFN-γ, and T-bet protein expressions in BMSC group and BMSCs +Notch inhibitor group all increased significantly, and Notch1 and Jagged1 protein expressions in BMSCs group and IL-5, IL-13, Notch1, and Jagged1 mRNA and protein expressions in BMSCs + Notch inhibitor group all decreased significantly (P<0.05 or 0.01). The expressions of CXCR4 and IFN-γ were significantly higher and the expressions of IL-13 and Notch1 mRNA were significantly lower in BMSCs+Notch inhibitor group than in BMSC group (P<0.05). Conclusion In asthmatic rats, the homing of the BMSCs to the lung tissue has a regulatory effect on Th1/Th2 drift, and the Notch1/Jagged1 pathway may participate in the homing of the BMSCs.

Key words: asthma; bone mesenchymal stem cells; homing; Th1/Th2 drift; Notch1/Jagged1 signaling pathway