title: Regulation of high glucose-mediated mucin expression by matrix metalloproteinase-9 in human airway epithelial cells.
abstract: Mucus hypersecretion is the key manifestation in patients with chronic inflammatory airway diseases and mucin 5AC (MUC5AC) is a major component of airway mucus. Matrix metalloproteinases (MMP)-9, have been found to be involved in the pathogenesis of inflammatory airway diseases. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that high glucose (HG)-regulates MMP-9 production and MMP-9 activity through nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS) cascades pathways, leading to mucin production in human airway epithelial cells (16HBE). We show that HG increases MMP-9 production, MMP-9 activity and MUC5AC expression. These effects are prevented by small interfering RNA (siRNA) for MMP-9, indicating that HG-induced mucin production is MMP-9-dependent. HG activates MMP-9 production, MMP-9 activity and MUC5AC overproduction, which is inhibited by nPG, DMSO and DPI (inhibitors of ROS and NADPH), suggesting that HG-activated mucin synthesis is mediated by NADPH/ROS in 16HBE cells. These observations demonstrate an important role for MMP-9 activated by NADPH/ROS signaling pathways in regulating HG-induced MUC5AC expression. These findings may bring new insights into the molecular pathogenesis of the infections related to diabetes mellitus and lead to novel therapeutic intervention for mucin overproduction in chronic inflammatory airway diseases.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing 400016, 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: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lü
authors.affiliation: Division of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Daijing
authors.initials: D
authors.lastname: Nie
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000201:enzymology*; D005947:Glucose / Q000502:physiology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology; D015533:Transcriptional Activation
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D017382:Reactive Oxygen Species; D009249:NADP; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D005947:Glucose
keywords: High glucose; MMP-9; Mucin; NADPH; ROS