Role of Brg1 in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia model.
10.7499/j.issn.1008-8830.2411078
- Author:
Ling GUAN
1
;
Mao-Zhu XU
1
;
Yao-Zheng LING
1
;
Li-Li YANG
1
;
Ling-Huan ZHANG
1
;
Sha LIU
1
;
Wen-Jing ZOU
1
;
Zhou FU
1
Author Information
1. Department of Respiratory Medicine/Children's Hospital of Chongqing Medical University/National Clinical Research Center for Child Health and Disorders/Ministry of Education Key Laboratory of Child Development and Disorders/Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
- Publication Type:Journal Article
- Keywords:
Alveolar type 2 epithelial cell;
Brahma-related gene 1;
Bronchopulmonary dysplasia;
Mouse;
Wnt/β-catenin signaling pathway
- MeSH:
Animals;
DNA Helicases/genetics*;
Transcription Factors/genetics*;
Wnt Signaling Pathway/physiology*;
Nuclear Proteins/genetics*;
Mice;
Bronchopulmonary Dysplasia/etiology*;
Mice, Inbred C57BL;
beta Catenin/physiology*;
Disease Models, Animal;
Cell Proliferation;
Lung/pathology*;
Male
- From:
Chinese Journal of Contemporary Pediatrics
2025;27(6):731-739
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES: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.
