YAP Promotes The Proliferation And Differentiation Of Lung Alveolar Epithelial Type ? Cells Partly Through The Wnt/?-catenin Signaling Pathway In BPD

Objective:Alveolar type II epithelial cells(AECIIs)are the most critical stem cells in lung tissue and play an important role in the recovery of bronchopulmonary dysplasia(BPD).Yes-associated protein(YAP)is an important transcriptional coactivator downstream of the Hippo signaling pathway,which regulates various stem cell biology and can be involved in regulating the proliferation and differentiation of AECIIs.YAP as an important transcription factor can regulate multiple pathways,including the wnt pathway,in which the wnt3a/?-catenin classical signaling pathway plays an important regulatory role in stabilizing alveolar structural morphology and promoting alveolar epithelial cell differentiation.BPD is a common severe pulmonary dysfunction in premature infants with the lung at the stage of cystic development,with high mortality.can show thickening of alveolar septum and simplification of alveolar structure pathologically.then whether YAP,Wnt3 a and ?-catenin are linked in the pathological case of BPD,and what mechanisms they are regulated by each other.Methods:The newborn rats were randomly divided into model group and control group within 24 hours after birth.BPD model was constructed in 85% oxygen to collect lung tissue at 1,3,7,14,and 21 days,respectively.lung tissue morphological changes were observed by microscope,through pcr,immunoblotting detection and immunofluorescence double staining.at the cellular level,primary AECIIs was extracted using plasmid overexpression YAP and silencing YAP to investigate whether it contributes to the proliferation and differentiation of AECIIs.Overexpression of Wnt3 a and knockdown of Wnt3 a were used to investigate whether YAP was involved in the proliferation and differentiation of AECIIs through the Wnt/?-catenin signaling pathway,and to collect the transcription and translation of relevant genes by PCR,immunoblotting and immunofluorescence detection.Results:In vivo experiment,the lung tissue of the experimental group gradually appeared alveolar septum thickening,alveolar spine disappeared,alveolar cavity increased,the number decreased,and the alveolar structure was simplified.the expression of YAP,Wnt3 a and ?-catenin in the lung tissues of the experimental group was significantly lower than that of normal lung tissues after 7 days(p <0.05),and SPC began to increase after 7 days(p <0.05),whereas the expression of AQP5decreased(p <0.05).In vitro experiments,when YAP was overexpressed(p <0.05),it promoted the proliferation of AECIIs and differentiation to AECIs(p <0.05),and vice versa.moreover,overexpression of YAP promoted nuclear transfer of ?-catenin(p<0.05)without effect on Wnt3a;Changes in expression of Wnt3a(p <0.05)reversed the effect of YAP on ?-catenin(p <0.05;)without altering its expression.Conclusion: YAP,Wnt3 a,and ?-catenin are all involved in the high oxygen-induced chronic lung injury chronic lung injury,especially the pathogenic process of alveolar injury,YAP and Wnt3 a are independent regulation of ?-catenin promote proliferation of AECIIs and the differentiation of AECIIs to AECIs,and YAP and Wnt3 a no regulating the relationship between each other,and YAP promotes the proliferation of AECIIs and the differentiation of AECIIs to AECIs by activating part of the wnt/?-catenin signaling pathway in the pathological process of chronic lung injury.Therefore,YAP may serve as a candidate regulatory target to improve AECIIs proliferation and differentiation in high oxygen-induced BPD.