Changes of protein kinase Calpha and cyclin D1 expressions in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease.
The purpose of this study was to investigate the changes of protein kinase Calpha (PKCalpha) and cyclin D1 expressions in pulmonary arteries from smokers with normal lung function and smokers with mild to moderate chronic obstructive pulmonary disease (COPD). The peripheral lung tissues were obtained from 10 non-smokers with normal lung function (non-smoker group), 14 smokers with normal lung function (smoker group), 11 smokers with mild to moderate COPD (COPD group). The morphological changes of pulmonary arteries were observed by HE-staining. The expressions of alpha-smooth muscle actin (alpha-SMA), proliferating cell nuclear antigen (PCNA), PKCalpha and cyclin D1 proteins in pulmonary artery smooth muscle cells (PASMCs) were immunohistochemically determined. The percentages of PCNA-positive cells were taken as the smooth muscle cells proliferation index (PI). The mRNA expressions of PKCalpha and cyclin D1 in PASMCs were evaluated by real-time fluorescence PCR. Morphometrical analysis showed that the ratio of pulmonary artery wall area to total area (WA%) in smoker group and COPD group was significantly greater than that in non-smoker group (P<0.01). The PASMCs proliferation index in smoker group and COPD group was significantly higher than that in nonsmoker group (P<0.01). The protein levels of PKCalpha and cyclin D1 in PASMCs were significantly increased in smoker group and COPD group as compared with non-smoker group (P<0.01). The mRNA expressions of PKCalpha and cyclin D1 in PASMCs were significantly elevated in smoker group and COPD group as compared with non-smoker group (P<0.01). Significant correlations were found between PKCalpha protein and WA% or PI (P<0.01). Correlations between cyclin D1 protein and WA% or PI also existed (P<0.01). The expression of PKCalpha was positively correlated with the expression of cyclin D1 at both protein and mRNA levels (P<0.01). In conclusion, increased expressions of PKCalpha and cyclin D1 might be involved in the pathogenesis of abnormal proliferation of PASMCs in smokers with normal lung function and smokers with mild to moderate COPD.
Xaing
Min
M
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. xiangmin166@gmail.com
Liu
Xiansheng
X
Zeng
Daxiong
D
Wang
Ran
R
Xu
Yongjian
Y
D000368:Aged; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000378:metabolism*
C530104:CCND1 protein, human; D012333:RNA, Messenger; D019938:Cyclin D1; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha
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