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Brg1 inhibits E-cadherin expression in lung epithelial cells and disrupts epithelial integrity

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Abstract

Brahma-related gene-1 (Brg1), a key chromatin remodeling factor, is associated with cell proliferation and migration in kidney and heart cells, but few reports have examined its role in airway epithelial cell. Airway epithelial injury, which is involved in the entire pathological process of asthma, is an important cause of recurrent asthma. Here, we studied the function of Brg1 in an ovalbumin (OVA)-induced asthma model (lung-specific conditional Brg1 (Brg1−/−) knockdown mice) and human bronchial epithelial 16HBE cells stably expressing Brg1 shRNA. Our results showed that high expression of Brg1 was detected in asthmatic children and in mouse models. Brg1−/− mice showed improved airway hyperresponsiveness (AHR) and bronchial epithelial integrity, along with reduced inflammatory cell infiltration and airway mucus secretion, when challenged with OVA. Furthermore, cell proliferation, migration, and expression of E-cadherin increased in 16HBE cells in which Brg1 was silenced. We further demonstrated that Brg1 bound to and inactivated a critical region (−86/+60 bp) within the E-cadherin promoter in bronchial epithelial cells. Thus, Brg1 might act as an important regulator of airway epithelial integrity in asthma progression and might be a novel therapeutic target.

Key messages

• Depletion of Brg1 improves the integrity of airway epithelium in asthma by regulating E-cadherin expression in lung epithelial cells.

• Knockdown of Brg1 increased the cell proliferation and migration by human bronchial epithelial 16HBE cells.

• Brg1 might bLLe a novel therapeutic target in asthma.

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Acknowledgements

This work was partially supported by grants from the National Natural Science Foundation of China (81670018, 81600022, 81070014), the Chongqing Municipal Health Bureau (2010-1-46), and the Chongqing Science and Technology Commission (cxtc2014yykfc10003).

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Author notes

  1. Ting Wang and Wenjing Zou equally contributed to the work.

Authors and Affiliations

  1. Pediatrics Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Ting Wang, Wenjing Zou, Chao Niu, Fengxia Ding, Yaping Wang, Shuang Cai, Hua Zhu, Daiyin Tian, Jihong Dai, Enmei Liu, Zhou Fu & Lin Zou

  2. Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, 136 Zhong Shan Er Rd, Chongqing, 400014, China

    Ting Wang, Wenjing Zou, Chao Niu, Fengxia Ding, Yaping Wang, Shuang Cai, Hua Zhu, Daiyin Tian, Jihong Dai, Enmei Liu & Zhou Fu

  3. West China Second Hospital, Sichuan University, Chengdu, China

    Qing Lu

  4. Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, 400014, China

    Zhou Fu & Lin Zou

  5. Center for Clinical Molecular Medicine, Children’s Hospital of Chongqing Medical University, 136 Zhong Shan Er Rd, Chongqing, 400014, China

    Lin Zou

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  1. Ting Wang
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Correspondence to Zhou Fu or Lin Zou.

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Wang, T., Zou, W., Niu, C. et al. Brg1 inhibits E-cadherin expression in lung epithelial cells and disrupts epithelial integrity. J Mol Med 95, 1117–1126 (2017). https://doi.org/10.1007/s00109-017-1576-7

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  • DOI: https://doi.org/10.1007/s00109-017-1576-7

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