Plasmid-based short hairpin RNA against cyclin D1 attenuated pulmonary vascular remodeling in smoking rats.
Accumulating evidence indicated that smoking might directly induce pulmonary vascular remodeling at the initial stage of chronic obstructive pulmonary disease (COPD). However, the molecular mechanism underlying this process remains poorly understood. To investigate the role of cyclin D1 in pulmonary vascular remodeling, we constructed a plasmid-based short hairpin RNA (shRNA) to knock down the expression of cyclin D1 in smoking rats. Specific shRNA against cyclin D1 significantly prevented the cyclin D1 expression and the cell proliferation in rat pulmonary artery smooth muscle cells (rPASMCs). Furthermore, the plasmid-based shRNA successfully decreased the cyclin D1 protein in intra-pulmonary arteries of smoking rats and subsequently decreased the wall thickness of pulmonary vessels and the percentage of muscularized vessels. We conclude that the plasmid-based shRNA against cyclin D1 gene attenuated pulmonary vascular remodeling in smoking rats. Cyclin D1 might play a critical role in cigarette smoke-induced pulmonary vascular remodeling via regulating rPASMCs proliferation.
Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Da-xiong
DX
Zeng
Xian-sheng
XS
Liu
Yong-jian
YJ
Xu
Ran
R
Wang
Min
M
Xiang
Wei-ning
WN
Xiong
Wang
W
Ni
Shi-xin
SX
Chen
D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D010957:Plasmids / Q000235:genetics; D011651:Pulmonary Artery / Q000503:physiopathology; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D014026:Nicotiana; D014162:Transfection
C530106:Ccnd1 protein, rat; D034741:RNA, Small Interfering; D012906:Smoke; D019938:Cyclin D1; D049452:Green Fluorescent Proteins