title: High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.
abstract: The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: yhm920@126.com.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yu
authors.affiliation: Division of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Respiratory Medicine, The Affiliated Hospital of Hainan Medical College, Hainan, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lü
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xia
mesh_terms: D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D010539:Permeability; D020545:Respiratory Mucosa / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D005947:Glucose
keywords: Airway epithelial integrity; Cx43; High glucose; Occludin; ZO-1