The Mechanism Of SDF-1/CXCR7 Axis Induced Mesenchymal Stem Cells Involved In Chronic Asthma Airway Remodeling

Objective:(1) By observing the expression of SDF-1 and CXCR7 among four groups, investigating the role of SDF-1 and CXCR7 on airway inflammation and airway remodeling in asthma. (2) Through watching after the transplanted bone marrow mesenchymal stem cells,the SDF-1 and CXCR7 expression in asthmatic rats, Discussion between the SDF-1/CXCR7 axis induced bone marrow mesenchymal stem cells involved in airway remodeling in rats.Methods:(1) The rats were sensitized and inhaled to induce asthma with ovalbumin (OVA) to make asthmatic model. After the success of models, measuring airway pressure. HE staining and pathology image analysis were used to detect the number of eosinophils (EOS), the perimeter inner, the wall area, the smooth muscle area, and the number of smooth muscle cells of airway wall. (2) After OVA inhalation four weeks, intravenous injection of GFP-BMSC, with the method of fluorescent immunohistochemistry to exploring BMSC migration. (3) RT-PCR and Western-blot were used to detect the expression of SDF-1 and CXCR7mRNA and protein in lung tissues among each groups. Immunohistochemistry was used to detect the expression of SDF-1 protein in airway wall in each groups. Counting data and investigating the association between the expression of SDF-1 and CXCR7 and asthma clinical features.Results:(1)Compared with control group, the number of EOS, the thickness of airway wall, in the asthmatic 4 weeks and asthmatic 8 weeks were significantly increased (P<0.01). With prolonged sensitized the above index gradually increased (P<0.01).②In asthmatic 8 weeks, the expression of SDF-1 and CXCR7mRNA in lung tissues were higher than asthmatic 4 weeks (P<0.01),In addition, the above indicators were higher than the normal group (P<0.01). Western blotting results also true. ③ Immunohistochemistry showed that comparing with control group, the expression of SDF-1 protein in airway wall in the asthmatic 4 weeks and asthmatic 8 weeks were significantly increased (P<0.01). In addition, compared with asthmatic 4 weeks, the above indicators in 8 weeks asthmatic were significantly increased (P<0.01). (2)①in asthma status, the bone marrow mesenchymal stem cells migrate to the lung tissue; And after blocking CXCR7, BMSC reduce migration② in asthma and BMSC transplanted groups, bronchial wall area, the area of airway smooth muscle, smooth muscle cells were significantly higher than those in normal control group (P<0.01), In addition,BMSC+block CXCR7 the index was significantly lower (P<0.01). ③RT-PCR showed that comparing with control group, the expression of SDF-1 and CXCR7mRNA in lung tissues in the asthma group and BMSC transplanted group,however, in BMSC+block CXCR7group,the expression of SDF-1 and CXCR7 mRNA also significantly reduced (P<0.01), but still higher than the normal group; Western blotting, immunohistochemistry test results consistent with the RT-PCR.Conclusions:(1) SDF-1/CXCR7 signaling axis may play an important role in the pathogenesis of airway inflammation and airway remodeling. (2) SDF-1/ CXCR7 axis would induced mesenchymal stem cells involved in chronic asthma airway pathological processes play an important role in remodeling.