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CARM1 regulates senescence during airway epithelial cell injury in COPD pathogenesis.
Am. J. Physiol. Lung Cell Mol. Physiol. 317, L602-L614 (2019)
Chronic obstructive pulmonary disease (COPD) is a life-threatening lung disease. Although cigarette smoke was considered the main cause of development, the heterogeneous nature of the disease leaves it unclear whether other factors contribute to the predisposition or impaired regeneration response observed. Recently, epigenetic modification has emerged to be a key player in the pathogenesis of COPD. The addition of methyl groups to arginine residues in both histone and nonhistone proteins by protein arginine methyltransferases (PRMTs) is an important posttranslational epigenetic modification event regulating cellular proliferation, differentiation, apoptosis, and senescence. Here, we hypothesize that coactivator-associated arginine methyltransferase-1 (CARM1) regulates airway epithelial cell injury in COPD pathogenesis by controlling cellular senescence. Using the naphthalene (NA)-induced mouse model of airway epithelial damage, we demonstrate that loss of CC10-positive club cells is accompanied by a reduction in CARM1-expressing cells of the airway epithelium. Furthermore, Carm1 haploinsuffficent mice showed perturbed club cell regeneration following NA treatment. In addition, CARM1 reduction led to decreased numbers of antisenescent sirtuin 1-expressing cells accompanied by higher p21, p16, and beta-galactosidase-positive senescent cells in the mouse airway following NA treatment. Importantly, CARM1-silenced human bronchial epithelial cells showed impaired wound healing and higher beta-galactosidase activity. These results demonstrate that CARM1 contributes to airway repair and regeneration by regulating airway epithelial cell senescence.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Airway Epithelium ; Carm1 ; Copd ; Senescence; Obstructive Lung-disease; Arginine Methylation; Gene-expression; Clara Cells; Methyltransferases; Proliferation; Differentiation; Activation; Mechanisms; Emphysema
ISSN (print) / ISBN
1040-0605
e-ISSN
1522-1504
Quellenangaben
Volume: 317,
Issue: 5,
Pages: L602-L614
Publisher
American Physiological Society
Publishing Place
Bethesda, Md. [u.a.]
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Reviewing status
Peer reviewed