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   Brg1 inhibits E-cadherin expression in lung epithelial cells and disrupts epithelial integrity  
   
نویسنده Wang Ting ,Zou Wenjing ,Niu Chao ,Ding Fengxia ,Wang Yaping ,Cai Shuang ,Zhu Hua ,Tian Daiyin ,Dai Jihong ,Liu Enmei ,Lu Qing ,Fu Zhou ,Zou Lin
منبع journal of molecular medicine - 2017 - دوره : 95 - شماره : 10 - صفحه:1117 -1126
چکیده    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. • 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.
کلیدواژه Asthma ,Epithelium ,Brg1 (Smarca4) ,E-cadherin
آدرس Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China. Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China, Sichuan University, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Children’s Hospital of Chongqing Medical University, Department of Respiratory Medicine, China. Chongqing Engineering Research Center of Stem Cell Therapy, China, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, China. Chongqing Engineering Research Center of Stem Cell Therapy, China. Children’s Hospital of Chongqing Medical University, China
 
     
   
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