Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
July-2017 Volume 14 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2017 Volume 14 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition

  • Authors:
    • Tao Guo
    • Xiangping Chai
    • Qiming Liu
    • Wen Peng
    • Zhenyu Peng
    • Yuzhong Cai
  • View Affiliations / Copyright

    Affiliations: Department of Emergency Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
    Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 214-220
    |
    Published online on: May 17, 2017
       https://doi.org/10.3892/etm.2017.4468
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The proliferation of vascular smooth muscle cells (VSMCs) serves an important role in cigarette smoking‑associated vascular diseases; however, the underlying mechanisms responsible for this remain unclear. The aim of the present study was to elucidate the role of P16 in cigarette smoke extract (CSE)‑induced VSMC proliferation and the underlying mechanism responsible. Human aortic smooth muscle cells (HAOSMCs) were exposed to CSE, and an MTT assay and flow cytometry were performed to evaluate cell proliferation and cell cycle distribution. Western blotting was conducted to examine protein expression and bisulfite genomic sequencing polymerase chain reaction was used to determine the methylation status of the P16 promoter CpG island. It was demonstrated that treatment with CSE significantly promoted the proliferation of HAOSMCs in a concentration‑ and time‑dependent manner and induced a downregulation in P16 expression (all P<0.05). A luciferase reporter gene assay data demonstrated that CSE treatment induced hypermethylation of the P16 promoter, which led to a significant decrease in its transcriptional activity and significantly reduced P16 protein expression in HAOSMCs (both P<0.01). Furthermore, P16 downregulation induced a significant increase in the expression of cyclin‑dependent kinase (CDK) 4, CDK6 and phosphorylated retinoblastoma (p‑Rb) protein (all P<0.001) and significantly increased the ratio of cells in S phase in CSE‑treated HAOSMCs (P<0.001). Overexpression of P16 inhibited CSE‑induced cell proliferation through inducing cell cycle arrest in G1 phase (P<0.001), and led to decreased levels of CDK4 (P<0.01), CDK6 (P<0.01) and p‑Rb (P<0.001) in HASMCs. The results of the present study therefore demonstrate that P16 may be associated with the CSE‑induced proliferation of VSMCs, suggesting that P16 serves a role in the development of cigarette smoke‑associated vascular diseases.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Ezzati M, Henley SJ, Thun MJ and Lopez AD: Role of smoking in global and regional cardiovascular mortality. Circulation. 112:489–497. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Ambrose JA and Barua RS: The pathophysiology of cigarette smoking and cardiovascular disease: An update. J Am Coll Cardiol. 43:1731–1737. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Burns DM: Epidemiology of smoking-induced cardiovascular disease. Prog Cardiovasc Dis. 46:11–29. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Hao H, Gabbiani G and Bochaton-Piallat ML: Arterial smooth muscle cell heterogeneity: Implications for atherosclerosis and restenosis development. Arterioscler Thromb Vasc Biol. 23:1510–1520. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Dzau VJ, Braun-Dullaeus RC and Sedding DG: Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies. Nat Med. 8:1249–1256. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Sherr CJ and Roberts JM: CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Malumbers M and Barbacid M: To cycle or not to cycle: A critical decision in cancer. Nat Rev Cancer. 1:222–231. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Burke JR, Hura GL and Rubin SM: Structures of inactive retinoblastoma protein reveal multiple mechanisms for cell cycle control. Genes Dev. 26:1156–1166. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Witkiewicz AK, Knudsen KE, Dicker AP and Knudsen ES: The meaning of p16(ink4a) expression in tumors: Functional significance, clinical associations and future developments. Cell Cycle. 10:2497–2503. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Rodriguez-Menocal L, Pham SM, Mateu D, St-Pierre M, Wei Y, Pestana I, Aitouche A and Vazquez-Padron RI: Aging increases p16 INK4a expression in vascular smooth-muscle cells. Biosci Rep. 30:11–18. 2019. View Article : Google Scholar

11 

Gizard F, Amant C, Barbier O, Bellosta S, Robillard R, Percevault F, Sevestre H, Krimpenfort P, Corsini A, Rochette J, et al: PPAR alpha inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a. J Clin Invest. 115:3228–3238. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Holdt LM and Teupser D: Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol. 32:196–206. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Holdt LM, Sass K, Gäbel G, Bergert H, Thiery J and Teupser D: Expression of Chr9p21 genes CDKN2B (p15(INK4b)), CDKN2A (p16(INK4a), p14(ARF)) and MTAP in human atherosclerotic plaque. Atherosclerosis. 214:264–270. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Yao Q, Xu H, Zhang QQ, Zhou H and Qu LH: MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells. Biochem Biophys Res Commun. 388:539–542. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Ou H, Shen YH, Utama B, Wang J, Wang X, Coselli J and Wang XL: Effect of nuclear actin on endothelial nitric oxide synthase expression. Arterioscler Thromb Vasc Biol. 25:2509–2514. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Motterle A, Pu X, Wood H, Xiao Q, Gor S, Ng FL, Chan K, Cross F, Shohreh B, Poston RN, et al: Functional analyses of coronary artery disease associated variation on chromosome 9p21 in vascular smooth muscle cells. Hum Mol Genet. 21:4021–4029. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Ghiorzo P, Villaggio B, Sementa AR, Hansson J, Platz A, Nicoló G, Spina B, Canepa M, Palmer JM, Hayward NK and Bianchi-Scarrà G: Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients. Hum Pathol. 35:25–33. 2004. View Article : Google Scholar : PubMed/NCBI

18 

LaPak KM and Burd CE: The molecular balancing act of p16(INK4a) in cancer and aging. Mol Cancer Res. 12:167–183. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Zhuang J, Peng W, Li H, Wang W, Wei Y, Li W and Xu Y: Methylation of p15INK4b and expression of ANRIL on chromosome 9p21 are associated with coronary artery disease. PLoS One. 7:e471932012. View Article : Google Scholar : PubMed/NCBI

20 

Miki K, Shimizu E, Yano S, Tani K and Sone S: Demethylation by 5-aza-2′-deoxycytidine (5-azadC) of p16INK4A gene results in downregulation of vascular endothelial growth factor expression in human lung cancer cell lines. Oncol Res. 12:335–342. 2001.PubMed/NCBI

21 

Elledge SJ: Cell cycle checkpoints: Preventing an identity crisis. Science. 274:1664–1672. 1996. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Guo T, Chai X, Liu Q, Peng W, Peng Z and Cai Y: Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition. Exp Ther Med 14: 214-220, 2017.
APA
Guo, T., Chai, X., Liu, Q., Peng, W., Peng, Z., & Cai, Y. (2017). Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition. Experimental and Therapeutic Medicine, 14, 214-220. https://doi.org/10.3892/etm.2017.4468
MLA
Guo, T., Chai, X., Liu, Q., Peng, W., Peng, Z., Cai, Y."Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition". Experimental and Therapeutic Medicine 14.1 (2017): 214-220.
Chicago
Guo, T., Chai, X., Liu, Q., Peng, W., Peng, Z., Cai, Y."Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition". Experimental and Therapeutic Medicine 14, no. 1 (2017): 214-220. https://doi.org/10.3892/etm.2017.4468
Copy and paste a formatted citation
x
Spandidos Publications style
Guo T, Chai X, Liu Q, Peng W, Peng Z and Cai Y: Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition. Exp Ther Med 14: 214-220, 2017.
APA
Guo, T., Chai, X., Liu, Q., Peng, W., Peng, Z., & Cai, Y. (2017). Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition. Experimental and Therapeutic Medicine, 14, 214-220. https://doi.org/10.3892/etm.2017.4468
MLA
Guo, T., Chai, X., Liu, Q., Peng, W., Peng, Z., Cai, Y."Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition". Experimental and Therapeutic Medicine 14.1 (2017): 214-220.
Chicago
Guo, T., Chai, X., Liu, Q., Peng, W., Peng, Z., Cai, Y."Downregulation of P16 promotes cigarette smoke extract‑induced vascular smooth muscle cell proliferation via preventing G1/S phase transition". Experimental and Therapeutic Medicine 14, no. 1 (2017): 214-220. https://doi.org/10.3892/etm.2017.4468
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team