title: Increased oxidative stress and disrupted small intestinal tight junctions in cigarette smoke-exposed rats.
abstract: Chronic obstructive pulmonary disease (COPD) is a major public health problem, and cigarette smoke (CS) is the primary risk factor. The pathology is often observed in the lung, but COPD is also associated with intestinal barrier disruption, although the underlying mechanisms are poorly understood. To address this, a CS‑exposed rat model was evaluated in the present study by analyzing small intestinal gene expression using reverse transcription‑quantitative polymerase chain reaction. CS exposure caused upregulation of the nicotinamide adenine dinucleotide phosphate‑oxidase subunits nox2 and p22phox in the small intestine, while the antioxidative enzyme superoxide dismutase was downregulated. CS exposure also increased bax expression and decreased bcl‑2 expression. This was associated with an elevation of hypoxia‑inducible factor (HIF)‑1α. Claudin‑1 was decreased and claudin‑2 increased, indicating a loosening of small intestinal tight junctions (TJs). These data suggest that during the development of COPD, HIF‑1α expression is altered in the small intestine, which may be associated with the increased oxidative stress and apoptosis, eventually resulting in disruption of the intestinal TJs.
authors.affiliation: Graduate School, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Graduate School, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Graduate School, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Respiratory Department, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Respiratory Department, Tianjin Institute of Respiratory Diseases, Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Huaiyong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D062445:Claudin-1 / Q000378:metabolism; D062446:Claudin-2 / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D062445:Claudin-1; D062446:Claudin-2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012906:Smoke; D051028:bcl-2-Associated X Protein; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C515768:Cyba protein, rat