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Objectives: To investigate the role and mechanism of Brahma-related gene 1 () in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model.
Methods: Wild-type C57BL/6 and mice were randomly divided into four groups: wild-type control, wild-type BPD, control, and BPD (=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and 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 control group and wild-type BPD group, the BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (<0.05). Compared to the control group, the 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 (<0.05). An interaction between Brg1 and β-catenin proteins was confirmed.
Conclusions: The 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234147 | PMC |
http://dx.doi.org/10.7499/j.issn.1008-8830.2411078 | DOI Listing |
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