title: Chronic obstructive sleep apnea accelerates pulmonary remodeling via TGF-β/miR-185/CoLA1 signaling in a canine model.
abstract: Chronic obstructive sleep apnea syndrome (OSAS) is considered to be associated with pulmonary diseases. However, the roles and mechanisms of OSA in pulmonary remodeling remain ambiguous. Thus, this study was aimed to elucidate the morphological and mechanical action of OSA in lung remodeling. In the present study, we employed a novel OSA model to mimic the OSA patient and investigate the role of OSA in pulmonary remodeling. We showed that pulmonary artery pressure of OSA group has no significant increased compared with the sham group. Nevertheless, we found that fibrotic tissue was predominantly located around the bronchi and vascular in the lung. Additionally, inflammatory cell infiltration was also detected in the peribonchial and perivascular space. The morphological change in OSA canines was ascertained by ultrastructure variation characterized by mitochondrial swelling, lamellar bodies degeneration and vascular smooth muscle incrassation. Moreover, sympathetic nerve sprouting was markedly increased in OSA group. Mechanistically, we showed that several pivotal proteins including collagen type I(CoLA1), GAP-43, TH and NGF were highly expressed in OSA groups. Furthermore, we found OSA could activated the expression of TGF-β, which subsequently suppressed miR-185 and promoted CoL A1 expression. This signaling cascade leads to pulmonary remodeling. In conclusion, Our data demonstrates that OSA can accelerate the progression of pulmonary remodeling through TGF-β/miR-185/CoLA1 signaling, which would potentially provide therapeutic strategies for chronic OSAS.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Dingyu
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Yun
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China.|Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, 150001, Heilongjiang Province, P. R. China.|Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 150001, Heilongjiang Province, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001980:Bronchi / Q000378:metabolism; D002460:Cell Line; D002908:Chronic Disease; D024042:Collagen Type I / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D007249:Inflammation; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D035683:MicroRNAs; D016212:Transforming Growth Factor beta
keywords: Pathology Section; canine model; chronic obstructive sleep apnea; molecular mechanisms; morphological change; transforming growth factor-beta1