2. Academic Validation
  3. MBD2 promotes epithelial-to-mesenchymal transition (EMT) and ARDS-related pulmonary fibrosis by modulating FZD2

MBD2 promotes epithelial-to-mesenchymal transition (EMT) and ARDS-related pulmonary fibrosis by modulating FZD2

  • Biochim Biophys Acta Mol Basis Dis. 2025 Mar 12;1871(5):167798. doi: 10.1016/j.bbadis.2025.167798.
Yang Zhou 1,  Guifang Yang 2,  Jiqiang Liu 2,  Shuo Yao 2,  Jingsi Jia 2,  Xianming Tang 2,  Xun Gong 2,  Fang Wan 2,  Ren Wu 3,  Zhenyu Zhao 4,  Hengxing Liang 5,  Linxia Liu 6,  Qimi Liu 6,  Shanshan Xie 7,  Xian Long 8,  Xudong Xiang 9,  Guyi Wang 10,  Bing Xiao 11
Affiliations

Affiliations

  • 1 Department of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, Hunan, China; Department of Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • 2 Department of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, Hunan, China.
  • 3 Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • 4 Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • 5 Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Thoracic Surgery, Guilin Hospital of the Second Xiangya Hospital of Central South University, Guilin, Guangxi, China.
  • 6 Department of Respiratory and Critical Care Medicine, Guilin Hospital of the Second Xiangya Hospital of Central South University, Guilin, Guangxi, China.
  • 7 Department of Emergency Medicine, Guilin Hospital of the Second Xiangya Hospital of Central South University, Guilin, Guangxi, China.
  • 8 Department of Clinic, Medicine School, Changsha Social Work College, Changsha, Hunan, China.
  • 9 Department of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, Hunan, China; Department of Respiratory and Critical Care Medicine, Guilin Hospital of the Second Xiangya Hospital of Central South University, Guilin, Guangxi, China.
  • 10 Department of Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address: yirengu@csu.edu.cn.
  • 11 Department of Emergency Medicine, Guilin Hospital of the Second Xiangya Hospital of Central South University, Guilin, Guangxi, China; Department of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, Hunan, China. Electronic address: xiaobing@csu.edu.cn.
PMID: 40081619 DOI: 10.1016/j.bbadis.2025.167798
Abstract

Objective: To investigate the role and underlying mechanism of Methyl-CpG binding domain protein 2 (MBD2) in the pathogenesis of acute respiratory distress syndrome (ARDS)-related pulmonary fibrosis.

Methods: Murine models for ARDS-related pulmonary fibrosis were established in wildtype or MBD2 knockout mice, expressions of MBD2 were determined with immunohistochemistry (IHC), immunofluorescence, and western blot. Epithelial-to-mesenchymal transition (EMT) was detected with determined with decreased expression of E-cadherin and increased expressions of N-Cadherin, Vimentin, and α-smooth muscle actin (α-SMA). Transforming growth factor β (TGF-β) treated mouse lung epithelial-12 (MLE-12) cells and primary human type II alveolar epithelial cells were applied to establish in vitro model for EMT. Transcriptional Sequencing with RNA-Seq and Chromatin immunoprecipitation (ChIP) assay were used to explore the potential targets of MBD2. Single cell Sequencing data and Human pulmonary fibrosis samples were analyzed.

Results: Bleomycin (BLM) and lipopolysaccharide (LPS) induced EMT, pulmonary fibrosis, and increased expression of MBD2 in alveolar epithelial cells of mice, and MBD2 knockout significantly alleviated BLM- and LPS-induced pulmonary fibrosis and EMT. TGF-β induced EMT and elevated MBD2 expressions in alveolar epithelial cells, which was mitigated by MBD2 knockdown and aggravated by MBD2 overexpression. Frizzled 2 (FZD2) was found to be the potential target of MBD2. Single-cell Sequencing analysis of ARDS patients suggested elevated expression of MBD2 in alveolar epithelial cells, and MBD2 expression was elevated in the lungs of patients with pulmonary fibrosis.

Conclusion: Our results indicated that MBD2 could promote EMT and ARDS-related pulmonary fibrosis, potentially by modulating the expression of FZD2.

Keywords

Acute respiratory distress syndrome (ARDS); Alveolar epithelial cell; Epithelial-to-mesenchymal transition (EMT); FZD2; Methyl-CpG binding domain protein 2 (MBD2); Pulmonary fibrosis.

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