Expression variations of connective tissue growth factor in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease

• Published in: Scientific reports 2015-02, Vol.5 (1), p.8564-8564, Article 8564
• Main Authors: Zhou, Si-jing, Li, Min, Zeng, Da-xiong, Zhu, Zhong-ming, Hu, Xian-Wei, Li, Yong-huai, Wang, Ran, Sun, Geng-yun
• Format: Article
• Language: English
• Subjects: 13/31; 13/89; 13/95; 38/88; 631/80/86/820; 692/699/75/593/1920; 82/80; Aged; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette smoking; Cigarettes; Connective tissue growth factor; Connective Tissue Growth Factor - antagonists & inhibitors; Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; Cyclin D1; Cyclin D1 - genetics; Cyclin D1 - metabolism; Down-Regulation - drug effects; E2F protein; E2F Transcription Factors - genetics; E2F Transcription Factors - metabolism; Growth factors; Humanities and Social Sciences; Humans; Hypertension; Lung - metabolism; Lung diseases; Middle Aged; mRNA; multidisciplinary; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - metabolism; Obstructive lung disease; pH effects; Pulmonary arteries; Pulmonary artery; Pulmonary Artery - metabolism; Pulmonary Artery - pathology; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - pathology; Real-Time Polymerase Chain Reaction; Respiratory function; RNA Interference; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Science; siRNA; Smoking - adverse effects; Smooth muscle; Up-Regulation - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep08564

Cigarette smoking contributes to the development of pulmonary hypertension (PH) complicated with chronic obstructive pulmonary disease (COPD) and the pulmonary vascular remodeling, the structural basis of PH, could be attributed to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs).In this study, morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than in nonsmokers. In addition, we determined the expression patterns of connective tissue growth factor (CTGF) and cyclin D1 in PASMCs harvested from smokers with normal lung function or mild to moderate COPD, finding that the expression levels of CTGF and cyclin D1 were significantly increased in smoker group and COPD group. In vitro experiment showed that the expression of CTGF, cyclin D1 and E2F were significantly increased in human PASMCs (HPASMCs) treated with 2% cigarette smoke extract (CSE) and two CTGF siRNAs with different mRNA hits successfully attenuated the upregulated cyclin D1 and E2F and significantly restored the CSE-induced proliferation of HPASMCs by causing cell cycle arrest in G0. These fndings suggest that CTGF may contribute to the pathogenesis of abnormal proliferation of HPASMCs by promoting the expression of its downstream effectors in smokers with or without COPD.