Research Papers: Pathology:

Chronic obstructive sleep apnea accelerates pulmonary remodeling via TGF-β/miR-185/CoLA1 signaling in a canine model

Xue Ding, Chengyuan Yu, Yang Liu, Sen Yan, Wenpeng Li, Dingyu Wang, Li Sun, Yu Han, Minghui Li, Song Zhang, Fengxiang Yun, Hongwei Zhao and Yue Li _

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Oncotarget. 2016; 7:57545-57555. https://doi.org/10.18632/oncotarget.11296

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Xue Ding1,*, Chengyuan Yu1,*, Yang Liu1, Sen Yan1, Wenpeng Li1, Dingyu Wang1, Li Sun1, Yu Han1, Minghui Li1, Song Zhang1, Fengxiang Yun1, Hongwei Zhao1 and Yue Li1,2,3

1 Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China

2 Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, 150001, Heilongjiang Province, P. R. China

3 Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 150001, Heilongjiang Province, P. R. China

* These authors have contributed equally to this paper

Correspondence to:

Yue Li, email:

Keywords: canine model; chronic obstructive sleep apnea; molecular mechanisms; morphological change; transforming growth factor-beta1; Pathology Section

Received: November 30, 2015 Accepted: August 03, 2016 Published: August 15, 2016


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.

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