Chronic obstructive sleep apnea accelerates pulmonary remodeling via TGF-β/miR-185/CoLA1 signaling in a canine model.
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.
['Ding|Xue|X|', 'Yu|Chengyuan|C|', 'Liu|Yang|Y|', 'Yan|Sen|S|', 'Li|Wenpeng|W|', 'Wang|Dingyu|D|', 'Sun|Li|L|', 'Han|Yu|Y|', 'Li|Minghui|M|', 'Zhang|Song|S|', 'Yun|Fengxiang|F|', 'Zhao|Hongwei|H|', 'Li|Yue|Y|']
D000818:Animals D001980:Bronchi D002460:Cell Line D002908:Chronic Disease D024042:Collagen Type I D004195:Disease Models, Animal D004285:Dogs D005786:Gene Expression Regulation D006801:Humans D006976:Hypertension, Pulmonary D007249:Inflammation D008168:Lung D008297:Male D035683:MicroRNAs D009131:Muscle, Smooth, Vascular D020181:Sleep Apnea, Obstructive D016212:Transforming Growth Factor beta
chronic obstructive sleep apnea canine model morphological change Pathology Section molecular mechanisms transforming growth factor-beta1