{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:21:56Z","timestamp":1791440516910,"version":"4.3.3"},"reference-count":64,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic obstructive pulmonary disease (COPD) is characterized by irreversible deterioration of the airway wall. Cigarette smoking is the major trigger, and in vitro studies showed that cigarette smoke extract (CSE) induced mitophagy in airway epithelial cells via oxidative stress, but this mechanism was not studied in airway smooth muscle cells (ASMCs). Primary ASMCs isolated from COPD patients or non-disease donors were investigated for CSE-induced remodeling and mitochondria structure. Proteins were assessed by Western blots for remodeling: collagen type-I, \u03b1-smooth muscle actin (\u03b1-SMA) and fibronectin; autophagy: beclin-1, protein62 (p62), light chain (LC)3A\/B; mitochondria activity: mitochondrially encoded cytochrome c oxidase II &amp; -IV (MTCO2, MTCO4), peroxisome proliferator activated receptor gamma coactivator 1\u03b1 (PGC-1\u03b1); lysosomes: early endosome antigen 1, lysosome activated membrane protein 1; and cell signaling: extracellular signal regulated kinase (ERK1\/2). Lysotracker and Mitotracker were used to monitor mitochondria morphology and organelle co-localization. Compared with controls, untreated COPD ASMCs showed lower collagen type-I and \u03b1-SMA expressions, but increased fibronectin levels. CSE further downregulated collagen type-I and \u03b1-SMA expression, but upregulated fibronectin. CSE decreased PGC-1\u03b1, MTCO2, and MTCO4, but increased beclin-1, p62, and LC3. CSE upregulated mitophagy and lysosomes activity via ERK1\/2 phosphorylation. In vitro, cigarette smoke induced the deterioration of ASMCs, which might explain the tissue loss and structural remodeling in COPD bronchi. The results suggest that preventing exceeded mitophagy in ASMCs might present a novel therapeutic target for COPD.<\/jats:p>","DOI":"10.3390\/ijms232213987","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:29:32Z","timestamp":1668392972000},"page":"13987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Airway Smooth Muscle Cell Mitochondria Damage and Mitophagy in COPD via ERK1\/2 MAPK"],"prefix":"10.3390","volume":"23","author":[{"given":"Lei","family":"Fang","sequence":"first","affiliation":[{"name":"Pulmonary Cell Research, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"},{"name":"Clinic of Respiratory Medicine, Department of Internal Medicine, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0794-2546","authenticated-orcid":false,"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pulmonary Cell Research, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"},{"name":"Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junling","family":"Li","sequence":"additional","affiliation":[{"name":"Pulmonary Cell Research, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"},{"name":"The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan 523000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pulmonary Cell Research, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"},{"name":"Clinic of Respiratory Medicine, Department of Internal Medicine, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tamm","sequence":"additional","affiliation":[{"name":"Pulmonary Cell Research, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"},{"name":"Clinic of Respiratory Medicine, Department of Internal Medicine, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8139-2821","authenticated-orcid":false,"given":"Michael","family":"Roth","sequence":"additional","affiliation":[{"name":"Pulmonary Cell Research, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"},{"name":"Clinic of Respiratory Medicine, Department of Internal Medicine, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s12272-021-01360-4","article-title":"Role of mitochondrial dynamics and mitophagy of vascular smooth muscle cell proliferation and migration in progression of atherosclerosis","volume":"44","author":"Huynh","year":"2021","journal-title":"Arch. 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