中国当代儿科杂志2025,Vol.27Issue(6):731-739,9.DOI:10.7499/j.issn.1008-8830.2411078
Brg1调控Wnt/β-catenin信号通路在支气管肺发育不良模型中的作用
Role of Brg1 in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia model
摘要
Abstract
Objective To investigate the role and mechanism of Brahma-related gene 1(Brg1)in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia(BPD)model.Methods Wild-type C57BL/6 and Brg1f1/f1 mice were randomly divided into four groups:wild-type control,wild-type BPD,Brg1f1/f1 control,and Brg1f1/f1 BPD(n=5 each).Immortalized mouse pulmonary alveolar type 2 cells(imPAC2)were cultured,and Brg1 gene was knocked down using lentivirus transfection technology.Cells were divided into three groups:control,empty vector,and Brg1 knockdown.Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue.Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue.Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox(HOPX),surfactant protein C(SPC),and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells.The CCK8 assay was used to assess the proliferation of imPAC2 cells,and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells.Results Compared to the Brg1f1/f1 control group and wild-type BPD group,the Brg1f1/f1 BPD group showed increased alveolar diameter and SPC protein expression,and decreased relative density of pulmonary vasculature and HOPX protein expression(P<0.05).Compared to the control group,the Brg1 knockdown group showed increased cell proliferation ability,protein expression levels of SPC,Wnt5a and β-catenin,and β-catenin protein fluorescence intensity,along with decreased HOPX protein expression(P<0.05).An interaction between Brg1 and β-catenin proteins was confirmed.Conclusions The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway,thus influencing the occurrence and development of BPD.关键词
支气管肺发育不良/Brahma相关基因1/Wnt/β-catenin信号通路/Ⅱ型肺泡上皮细胞/小鼠Key words
Bronchopulmonary dysplasia/Brahma-related gene 1/Wnt/β-catenin signaling pathway/Alveolar type 2 epithelial cell/Mouse引用本文复制引用
官玲,徐茂竹,凌耀政,杨丽丽,张龄幻,刘莎,邹文静,符州..Brg1调控Wnt/β-catenin信号通路在支气管肺发育不良模型中的作用[J].中国当代儿科杂志,2025,27(6):731-739,9.基金项目
重庆市自然科学基金面上项目(CSTB2022NSCQ-MSX0871). (CSTB2022NSCQ-MSX0871)