title: Knockdown of connective tissue growth factor by plasmid-based short hairpin RNA prevented pulmonary vascular remodeling in cigarette smoke-exposed rats.
abstract: Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by resulting in pulmonary vascular remodeling that involves pulmonary artery smooth muscle cell proliferation. Connective tissue growth factor (CTGF) is a cysteine-rich peptide implicated in several biological processes such as cell proliferation, survival, and migration. This study investigated the potential role of CTGF in pulmonary vascular remodeling. We constructed a plasmid-based short hairpin RNA (shRNA) to knock down the expression of CTGF in primary cultured rat pulmonary artery smooth muscle cells (rPASMCs) and in rat lung vessels. Rat PASMCs were challenged with cigarette smoke extract (CSE). Rats were exposed to cigarette smoke for 3 months in the absence or in the presence of plasmid-based short hairpin RNA against CTGF which was administrated by tail vein injection. CTGFshRNA significantly prevented CTGF and cyclin D1 expression, arrested cell cycle at G0/G1 phase and suppressed cell proliferation in rPASMCs exposed to CSE. CTGFshRNA administration ameliorated pulmonary vascular remodeling, inhibited cigarette smoke-induced CTGF elevation and reversed the cyclin D1 increase in pulmonary vessels in rats. Collectively, our data demonstrated that plasmid-based shRNA against CTGF attenuated pulmonary vascular remodeling in cigarette smoke-exposed rats.
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Xu
authors.forename: Xian-Sheng
authors.initials: XS
authors.lastname: Liu
authors.forename: Da-Xiong
authors.initials: DX
authors.lastname: Zeng
authors.forename: Min
authors.initials: M
authors.lastname: Xiang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D055513:Connective Tissue Growth Factor / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010957:Plasmids / Q000235:genetics*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016196:S Phase / Q000187:drug effects / Q000235:genetics; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects / Q000737:chemistry; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
chemical_list: C526316:CCN2 protein, rat; D034741:RNA, Small Interfering; D012906:Smoke; D019938:Cyclin D1; D055513:Connective Tissue Growth Factor