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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
April-2020 Volume 21 Issue 4

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
April-2020 Volume 21 Issue 4

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

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes

  • Authors:
    • Xinxin Liu
    • Xin Wang
    • Nian Liu
    • Ke Zhu
    • Song Zhang
    • Xiaoru Duan
    • Yuqiong Huang
    • Zilin Jin
    • Himanshu Jaypaul
    • Yan Wu
    • Hongxiang Chen
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hebei 430022, P.R. China, Department of Dermatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1941-1949
    |
    Published online on: February 18, 2020
       https://doi.org/10.3892/mmr.2020.10989
  • 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

DNA methylation and hydroxymethylation are the most common epigenetic modifications associated with the cell cycle and the inflammatory response. The present study aimed to investigate the role of 5‑hydroxymethyl‑cytosine (5‑hmC) and ten‑eleven translocation‑2 (TET2) in keratinocytes. Following TET2 knockdown, dot blot analysis was performed to assess the levels of 5‑hmC in keratinocytes, using HaCaT cells. Subsequently, the viability and cell cycle of HaCaT cells were assessed by MTT, Cell Counting Kit‑8 assay and flow cytometric assays. Cyclin‑dependent kinase inhibitor 2A and proinflammatory cytokine protein and mRNA expression levels were also detected. The present results suggested that TET2 may play an important role in regulating cellular proliferation by mediating DNA hydroxymethylation in HaCaT cells. In addition, TET2 knockdown decreased the production of proinflammatory cytokines, including lipocalin 2, S100 calcium binding protein A7, matrix metallopeptidase 9, C‑X‑C motif chemokine ligand 1, interferon regulatory factor 7 and interleukin‑7 receptor. The present study suggested that TET2 regulated cell viability, apoptosis and the expression of inflammatory mediators in keratinocytes. Collectively, the results indicated that TET2 knockdown may relieve inflammatory responses in the skin.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Shen J, Abu-Amer Y, O'Keefe RJ and McAlinden A: Inflammation and epigenetic regulation in osteoarthritis. Connect Tissue Res. 58:49–63. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Wu X and Zhang Y: TET-mediated active DNA demethylation: Mechanism, function and beyond. Nat Rev Genet. 18:517–534. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Li D, Guo B, Wu H, Tan L and Lu Q: TET family of dioxygenases: Crucial roles and underlying mechanisms. Cytogenet Genome Res. 146:171–180. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Hu L, Li Z, Cheng J, Rao Q, Gong W, Liu M, Shi YG, Zhu J, Wang P and Xu Y: Crystal structure of TET2-DNA complex: Insight into TET-mediated 5mC oxidation. Cell. 155:1545–1555. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Ichiyama K, Chen T, Wang X, Yan X, Kim BS, Tanaka S, Ndiaye-Lobry D, Deng Y, Zou Y, Zheng P, et al: The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells. Immunity. 42:613–626. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Pastor WA, Aravind L and Rao A: TETonic shift: Biological roles of TET proteins in DNA demethylation and transcription. Nat Rev Mol Cell Biol. 14:341–356. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C and Zhang Y: Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 333:1300–1303. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Rasmussen KD and Helin K: Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev. 30:733–750. 2016. View Article : Google Scholar : PubMed/NCBI

9 

He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, et al: Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 333:1303–1307. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Weber AR, Krawczyk C, Robertson AB, Kuśnierczyk A, Vågbø CB, Schuermann D, Klungland A and Schär P: Biochemical reconstitution of TET1-TDG-BER-dependent active DNA demethylation reveals a highly coordinated mechanism. Nat Commun. 7:108062016. View Article : Google Scholar : PubMed/NCBI

11 

Zhang Q, Zhao K, Shen Q, Han Y, Gu Y, Li X, Zhao D, Liu Y, Wang C, Zhang X, et al: Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature. 525:389–393. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Li X, Yao B, Chen L, Kang Y, Li Y, Cheng Y, Li L, Lin L, Wang Z, Wang M, et al: Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis. Nat Commun. 8:159032017. View Article : Google Scholar : PubMed/NCBI

13 

Sun H, Miao Z, Wang H, Tao Y, Yang J, Cai J, Wang J and Wang Y: DNA hydroxymethylation mediated traumatic spinal injury by influencing cell death-related gene expression. J Cell Biochem. 119:9295–9302. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Uchiyama R, Uhara H, Uchiyama A, Ogawa E, Takazawa Y, Ashida A, Koga H, Hayashi K, Kiniwa Y and Okuyama R: 5-Hydroxymethylcytosine as a useful marker to differentiate between malignant melanomas and benign melanocytic nevi. J Dermatol Sci. 73:161–163. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Benhadou F, Mintoff D and Del Marmol V: Psoriasis: Keratinocytes or immune cells - Which is the trigger? Dermatology. 235:91–100. 2019. View Article : Google Scholar : PubMed/NCBI

16 

Bitschar K, Wolz C, Krismer B, Peschel A and Schittek B: Keratinocytes as sensors and central players in the immune defense against Staphylococcus aureus in the skin. J Dermatol Sci. 87:215–220. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Asahina R and Maeda S: A review of the roles of keratinocyte-derived cytokines and chemokines in the pathogenesis of atopic dermatitis in humans and dogs. Vet Dermatol. 28:16–e5. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Fogel O, Richard-Miceli C and Tost J: Epigenetic changes in chronic inflammatory diseases. Adv Protein Chem Struct Biol. 106:139–189. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Wang X, Liu X, Liu N and Chen H: Prediction of crucial epigenetically-associated, differentially expressed genes by integrated bioinformatics analysis and the identification of S100A9 as a novel biomarker in psoriasis. Int J Mol Med. 45:93–102. 2020.PubMed/NCBI

21 

Poole CJ, Lodh A, Choi JH and van Riggelen J: MYC deregulates TET1 and TET2 expression to control global DNA (hydroxy)methylation and gene expression to maintain a neoplastic phenotype in T-ALL. Epigenetics Chromatin. 12:412019. View Article : Google Scholar : PubMed/NCBI

22 

Chiba S: Dysregulation of TET2 in hematologic malignancies. Int J Hematol. 105:17–22. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Raghuraman S, Donkin I, Versteyhe S, Barrès R and Simar D: The emerging role of epigenetics in inflammation and immunometabolism. Trends Endocrinol Metab. 27:782–795. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Wang X, Liu X, Duan X, Zhu K, Zhang S, Gan L, Liu N, Jaypaul H, Makamure JT, Ming Z, et al: Ten-eleven translocation-2 regulates DNA hydroxymethylation status and psoriasiform dermatitis progression in mice. Acta Derm Venereol. 98:585–593. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Cheng X and Blumenthal RM: Mammalian DNA methyltransferases: A structural perspective. Structure. 16:341–350. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Ko M, An J, Bandukwala HS, Chavez L, Aijö T, Pastor WA, Segal MF, Li H, Koh KP, Lähdesmäki H, et al: Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX. Nature. 497:122–126. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Prikrylova T, Robertson J, Ferrucci F, Konorska D, Aanes H, Manaf A, Zhang B, Vågbø CB, Kuśnierczyk A, Gilljam KM, et al: 5-hydroxymethylcytosine marks mammalian origins acting as a barrier to replication. Sci Rep. 9:110652019. View Article : Google Scholar : PubMed/NCBI

28 

Chrysanthou S, Senner CE, Woods L, Fineberg E, Okkenhaug H, Burge S, Perez-Garcia V and Hemberger M: A critical role of TET1/2 proteins in cell-cycle progression of trophoblast stem cells. Stem Cell Reports. 10:1355–1368. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Shimozaki K: Ten-eleven translocation 1 and 2 confer overlapping transcriptional programs for the proliferation of cultured adult neural stem cells. Cell Mol Neurobiol. 37:995–1008. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Mahfoudhi E, Talhaoui I, Cabagnols X, Della Valle V, Secardin L, Rameau P, Bernard OA, Ishchenko AA, Abbes S, Vainchenker W, et al: TET2-mediated 5-hydroxymethylcytosine induces genetic instability and mutagenesis. DNA Repair (Amst). 43:78–88. 2016. View Article : Google Scholar : PubMed/NCBI

31 

O'Neill CJ and McCluggage WG: p16 expression in the female genital tract and its value in diagnosis. Adv Anat Pathol. 13:8–15. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Aagaard L, Lukas J, Bartkova J, Kjerulff AA, Strauss M and Bartek J: Aberrations of p16Ink4 and retinoblastoma tumour-suppressor genes occur in distinct sub-sets of human cancer cell lines. Int J Cancer. 61:115–120. 1995. View Article : Google Scholar : PubMed/NCBI

33 

Stylianou E: Epigenetics of chronic inflammatory diseases. J Inflamm Res. 12:1–14. 2018. View Article : Google Scholar : PubMed/NCBI

34 

Lagos C, Carvajal P, Castro I, Jara D, González S, Aguilera S, Barrera MJ, Quest AFG, Bahamondes V, Molina C, et al: Association of high 5-hydroxymethylcytosine levels with Ten Eleven Translocation 2 overexpression and inflammation in Sjögren's syndrome patients. Clin Immunol. 196:85–96. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Wang X, Feng Z, Li Q, Yi B and Xu Q: DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation. Cell Tissue Res. 373:477–485. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu X, Wang X, Liu N, Zhu K, Zhang S, Duan X, Huang Y, Jin Z, Jaypaul H, Wu Y, Wu Y, et al: TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes. Mol Med Rep 21: 1941-1949, 2020.
APA
Liu, X., Wang, X., Liu, N., Zhu, K., Zhang, S., Duan, X. ... Chen, H. (2020). TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes. Molecular Medicine Reports, 21, 1941-1949. https://doi.org/10.3892/mmr.2020.10989
MLA
Liu, X., Wang, X., Liu, N., Zhu, K., Zhang, S., Duan, X., Huang, Y., Jin, Z., Jaypaul, H., Wu, Y., Chen, H."TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes". Molecular Medicine Reports 21.4 (2020): 1941-1949.
Chicago
Liu, X., Wang, X., Liu, N., Zhu, K., Zhang, S., Duan, X., Huang, Y., Jin, Z., Jaypaul, H., Wu, Y., Chen, H."TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes". Molecular Medicine Reports 21, no. 4 (2020): 1941-1949. https://doi.org/10.3892/mmr.2020.10989
Copy and paste a formatted citation
x
Spandidos Publications style
Liu X, Wang X, Liu N, Zhu K, Zhang S, Duan X, Huang Y, Jin Z, Jaypaul H, Wu Y, Wu Y, et al: TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes. Mol Med Rep 21: 1941-1949, 2020.
APA
Liu, X., Wang, X., Liu, N., Zhu, K., Zhang, S., Duan, X. ... Chen, H. (2020). TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes. Molecular Medicine Reports, 21, 1941-1949. https://doi.org/10.3892/mmr.2020.10989
MLA
Liu, X., Wang, X., Liu, N., Zhu, K., Zhang, S., Duan, X., Huang, Y., Jin, Z., Jaypaul, H., Wu, Y., Chen, H."TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes". Molecular Medicine Reports 21.4 (2020): 1941-1949.
Chicago
Liu, X., Wang, X., Liu, N., Zhu, K., Zhang, S., Duan, X., Huang, Y., Jin, Z., Jaypaul, H., Wu, Y., Chen, H."TET2 is involved in DNA hydroxymethylation, cell proliferation and inflammatory response in keratinocytes". Molecular Medicine Reports 21, no. 4 (2020): 1941-1949. https://doi.org/10.3892/mmr.2020.10989
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