The Role Of Follistatin-like Protein 1 In TGF-β/Smads Mediated Airway Mucus Hypersecretion In Asthmatic Mice

Objective: To observe the effect of follistatin-like protein 1(FSTL1)monoclonal antibody 22B6 m Ab intervention on airway mucus hypersecretion in asthmatic mice,and to explore the role and mechanism of FSTL1 in asthmatic airway mucus hypersecretion.Methods: Thirty 6-8-week-old SPF female BALB/c mice were randomly divided into normal group(NS group),asthma group(AS group),and FSTL1 monoclonal antibody 22B6 m Ab group(m Ab group),10 mice in each group.AS group was sensitized by intraperitoneal injection of 10% ovalbumin(OVA)aluminum hydroxide gel combined with subcutaneous injection on the 1st and 13 th days of the experiment.1 time,30 min each time.The NS group was sensitized and challenged with PBS and normal saline instead of OVA,respectively.The m Ab group was intervened by intraperitoneal injection of 20 ug of 22B6 m Ab 30 min before each nebulization challenge,and the rest of the treatments were the same as those in the AS group.Mice in each group were sacrificed 24 hours after the last challenge,and bronchoalveolar lavage fluid(BALF)and lung tissue samples were prepared.The BALF of each group was subjected to total cell count and differential white blood cell count,and ELISA was used to detect the concentrations of FSTL1,IL-10 and IL-17 in BLAF;the lung tissue was subjected to HE staining,AB-PAS staining and Masson staining to observe the pathological changes of lung tissue.The protein expression levels of Muc5 ac,FSTL1,TGF-β1,Smad2 and Smad3 in lung tissue were observed by IHC,and the relative expression levels of FSTL1 and Muc5 ac m RNA in lung tissue were detected by RT-PCR.Results:Compared with the NS group,the total number of BALF cells,the percentage of eosinophils,the concentrations of IL-17 and FSTL1 in the AS group were all increased(P<0.01),the IL-10 concentration in the BALF was decreased(P<0.01),and the lung tissue gas The thickness of the airway wall,the infiltration score of inflammatory cells around the airway,the positive relative staining area of airway mucous substances and the airway collagen fiber deposition area were all increased(P<0.01).Compared with the AS group,the IL-10 concentration in the BALF of the m Ab group was increased(P<0.01),and the other indexes were all decreased(P<0.01).Conclusion: 22B6 m Ab intervention can inhibit the hypersecretion of airway mucus in asthma,and the mechanism may be through inhibiting the expression of FSTL1,reducing airway inflammation and up-regulating the TGF-β/Smads signaling pathway,resulting in the decrease of airway mucus secretion.