Role of Brg1 in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia model

Ling GUAN, Mao-Zhu XU, Yao-Zheng LING, Li-Li YANG, Ling-Huan ZHANG, Sha LIU, Wen-Jing ZOU, Zhou FU

Chinese Journal of Contemporary Pediatrics ›› 2025, Vol. 27 ›› Issue (6) : 731-739.

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Chinese Journal of Contemporary Pediatrics ›› 2025, Vol. 27 ›› Issue (6) : 731-739. DOI: 10.7499/j.issn.1008-8830.2411078
EXPERIMENTAL RESEARCH

Role of Brg1 in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia model

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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.

Key words

Bronchopulmonary dysplasia / Brahma-related gene 1 / Wnt/β-catenin signaling pathway / Alveolar type 2 epithelial cell / Mouse

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Ling GUAN , Mao-Zhu XU , Yao-Zheng LING , et al . Role of Brg1 in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia model[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(6): 731-739 https://doi.org/10.7499/j.issn.1008-8830.2411078

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