Wang Kun, Zhu Huizhi, Yang Lei, Xu Qingwen, Ren Fengchun
Graduate School, Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
First Affiliated Hospital, Anhui University of Traditional Chinese Medicine, Hefei 230031, China. *Corresponding author, E-mail:
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2021 Feb;37(2):97-104.
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.
目的 研究微小RNA-139（miR-139）调控Notch信号通路对骨髓间充质干细胞（BMSCs）归巢及哮喘气道炎症的影响。方法 将24只SD大鼠随机分为正常对照组、模型对照组和BMSCs组。对大鼠进行卵清蛋白激发，然后将BMSCs移植入大鼠体内。通过苏木精-伊红（HE）染色观察肺组织病理变化。采用流式细胞术检测肺组织中BMSCs标志物C-X-C基序趋化因子受体4（CXCR4）的表达，通过免疫荧光染色观察支气管上皮细胞中CXCR4的表达。采用酶联免疫吸附测定（ELISA）法检测干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）的表达，通过蛋白质免疫印迹分析检测肺组织中Notch1、Jagged1和Hes1的表达。结果 与正常对照组相比，模型对照组肺组织中CXCR4、IL-4、Notch1和Hes1的表达显著增加，Th1/Th2细胞比值及miR-139 mRNA水平降低。与模型对照组相比，BMSCs组肺组织及支气管上皮细胞中CXCR4的表达增加，Th1/Th2细胞比值及miR-139 mRNA水平升高，而Notch1和Hes1的表达降低。相关性分析显示，肺组织中CXCR4的表达与支气管上皮细胞中CXCR4的表达、Th1/Th2细胞比值及miR-139呈正相关。支气管上皮细胞中CXCR4的表达与Th1/Th2细胞比值、miR-139的表达呈正相关，与Notch1的表达呈负相关。Th1/Th2细胞比值与miR-139的表达呈正相关。结论 miR-139可下调Notch通路，促进BMSCs在哮喘肺组织中的归巢，从而通过免疫调节抑制Th2细胞的炎症反应。
