title: Reduced nuclear translocation of serum response factor is associated with skeletal muscle atrophy in a cigarette smoke-induced mouse model of COPD.
abstract: Skeletal muscle atrophy and dysfunction are common complications in the chronic obstructive pulmonary disease (COPD). However, the underlying molecular mechanism remains elusive. Serum response factor (SRF) is a transcription factor which is critical in myocyte differentiation and growth. In this study, we established a mouse COPD model induced by cigarette smoking (CS) exposure for 24 weeks, with apparent pathophysiological changes, including increased airway resistance, enlarged alveoli, and skeletal muscle atrophy. Levels of upstream regulators of SRF, striated muscle activator of Rho signaling (STARS), and ras homolog gene family, member A (RhoA) were decreased in quadriceps muscle of COPD mice. Meanwhile, the nucleic location of SRF was diminished along with its cytoplasmic accumulation. There was a downregulation of the target muscle-specific gene,Igf1. These results suggest that the CS is one of the major causes for COPD pathogenesis, which induces the COPD-associated skeletal muscle atrophy which is closely related to decreasing SRF nucleic translocation, consequently downregulating the SRF target genes involved in muscle growth and nutrition. The STARS/RhoA signaling pathway might contribute to this course by impacting SRF subcellular distribution.
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Ma
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Gong
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Lin
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Chenting
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Wenju
authors.initials: W
authors.lastname: Lu
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000378:metabolism; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D052097:Quadriceps Muscle / Q000378:metabolism* / Q000473:pathology; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: C518897:Abra protein, mouse; D008840:Microfilament Proteins; D026362:Serum Response Factor; D012906:Smoke; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: SRF; chronic obstructive pulmonary disease; cigarette smoking; skeletal muscle atrophy