Skip to main content
Log in

Changes of protein kinase Cα and cyclin D1 expressions in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

The purpose of this study was to investigate the changes of protein kinase Cα (PKCα) 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 α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), PKCα 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 PKCα 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 PKCα 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 PKCα 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 PKCα 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 PKCα was positively correlated with the expression of cyclin D1 at both protein and mRNA levels (P<0.01). In conclusion, increased expressions of PKCα 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Santos S, Peinado VI, Ramirez J, et al. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. Eur Respir J, 2002,19(4):632–638

    Article  CAS  PubMed  Google Scholar 

  2. Wright JL, Churg A. Effect of long-term cigarette smoke exposure on pulmonary vascular structure and function in the guinea pig. Exp lung Res, 1991,17(6):997–1009

    Article  CAS  PubMed  Google Scholar 

  3. Ferrer E, Peinado VI, Diez M, et al. Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig. Respir Res, 2009,10:76

    Article  PubMed  Google Scholar 

  4. Wang S, Desai D, Wright G, et al. Effects of protein kinase C alpha overexpression on A7r5 smooth muscle cell proliferation and differentiation. Exp Cell Res, 1997, 236(1):117–126

    Article  CAS  PubMed  Google Scholar 

  5. Grillo M, Bott MJ, Khandke N, et al. Validation of cyclin D1/CDK4 as an anticancer drug target in MCF-7 breast cancer cells:Effect of regulated overexpression of cyclin D1 and siRNA-mediated inhibition of endogenous cyclin D1 and CDK4 expression. Breast Cancer Res Treat, 2006, 95(2):185–194

    Article  CAS  PubMed  Google Scholar 

  6. Qiao LF, Xu YJ, Liu XS, et al. Role of protein Cα and cyclin D1 in the profileration of airway smooth muscle in asthmatic rats. Chin Med J, 2008,121(20):2070–2076

    CAS  PubMed  Google Scholar 

  7. Hu J, Xu YJ, Zhang ZY, et al. Effect of cigarette smoke extract on proliferation of human pulmonary artery smooth muscle cells and the relevant roles of protein kinase C. Acta Med Univ Sci Technol Huazhong (Chinese), 2008,37(3):281–285

    CAS  Google Scholar 

  8. Chronic obstructive pulmonary disease study group in Chinese Society of Respiratory Diseases. Diagnosis and treatment guidelines of chronic obstructive pulmonary disease. Chin J Intern Med (Chinese), 2007,46(3):254–261

    Google Scholar 

  9. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J, 2008,32(5): 1371–1385

    Article  CAS  PubMed  Google Scholar 

  10. Pullamsetti S, Krick S, Yilmaz H, et al. Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration. Respir Res, 2005,6:128

    Article  PubMed  Google Scholar 

  11. Mandegar M, Fung YC, Huang W, et al. Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. Microvasc Res, 2004,68(2):75–103

    Article  CAS  PubMed  Google Scholar 

  12. Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature, 1988,334(6184):661–665

    Article  CAS  PubMed  Google Scholar 

  13. Malhotra A, Kang BP, Opawumi D, et al. Molecular biology of protein kinase C signaling in cardiac myocytes. Mol Cell Biochem, 2001,225(1-):97–107

    Article  CAS  PubMed  Google Scholar 

  14. Berkenbosch JW, Baribeau J, Ferretti E, et al. Role of protein kinase C and phosphatases in the vasculature of neonatal piglets. Crit Care Med, 2001,29(6):1229–1233

    Article  CAS  PubMed  Google Scholar 

  15. Dempsey EC, Frid MG, Aldashev AA, et al. Heterogeneity in the proliferative response of bovine pulmonary artery smooth muscle cells to mitogens and hypoxia: importance of protein kinase C. Can J Physiol Pharmacol, 1997,75(7): 936–944

    Article  CAS  PubMed  Google Scholar 

  16. Okazaki J, Mawatari K, Liu B, et al. The effect of protein kinase C and its alpha subtype on human vascular smooth muscle cell proliferation, migration and fibronectin production. Surgery, 2000,128(2):192–197

    Article  CAS  PubMed  Google Scholar 

  17. Grillo M, Bott MJ, Khandke N, et al. Validation of cyclin D1/CDK4 as an anticancer drug target in MCF-7 breast cancer cells: Effect of regulated overexpression of cyclin D1 and siRNA-mediated inhibition of endogenous cyclin D1 and CDK4 expression. Breast Cancer Res Treat, 2006, 95(2):185–194

    Article  CAS  PubMed  Google Scholar 

  18. Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev, 1998,12(15):2245–2262

    Article  CAS  PubMed  Google Scholar 

  19. Imoto M, Tanabe K, Simizu S, et al. Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cells. Jpn J Cancer Res, 1998,89(3):315–322

    CAS  PubMed  Google Scholar 

  20. Marsit CJ, Black CC, Posner MR, et al. A genotype-phenotype examination of cyclin D1 on risk and outcome of squamous cell carcinoma of the head and neck. Clin Cancer Res, 2008,14(8):2371–2377

    Article  CAS  PubMed  Google Scholar 

  21. Zhang YM, Wang KQ, Zhou GM, et al. Endothelin-1 promoted proliferation of vascular smooth muscle cell through pathway of extracellular signal-regulated kinase and cyclin D1. Acta Pharmacol Sin, 2003,24(6):563–568

    CAS  PubMed  Google Scholar 

  22. Lee SD, Lee DS, Chun YG, et al. Cigarette smoke extract induces endothelin-1 via protein kinase C in pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol, 2001,281(2):L403–L411

    CAS  PubMed  Google Scholar 

  23. Black JD. Protein kinase C-mediated regulation of the cell cycle. Front Biosci, 2000,5:D406–D423

    Article  CAS  PubMed  Google Scholar 

  24. Lai Y, Li W. Expression and clinical significance of mucoprotenin MUC5AC in patients with chronic obstructive pulmonary disease. Acta Med Univ Sci Technol Huazhong (Chinese), 2009,38(3):385–388

    CAS  Google Scholar 

  25. Soh JW, Weinstein IB. Roles of specific isoforms of protein kinase C in the transcriptional control of cyclin D1 and related genes. J Biol Chem, 2003,278(36):34709–34716

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yongjian Xu  (徐永健).

Additional information

This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30871128).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xaing, M., Liu, X., Zeng, D. et al. Changes of protein kinase Cα and cyclin D1 expressions in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 30, 159–164 (2010). https://doi.org/10.1007/s11596-010-0205-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-010-0205-2

Key words

Navigation