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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
June-2015 Volume 35 Issue 6

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
June-2015 Volume 35 Issue 6

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

miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling

  • Authors:
    • Honghui He
    • Ke Chen
    • Fang Wang
    • Liling Zhao
    • Xinxing Wan
    • Linghao Wang
    • Zhaohui Mo
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1587-1595
    |
    Published online on: March 31, 2015
       https://doi.org/10.3892/ijmm.2015.2160
  • 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

MicroRNAs (miRNAs or miRs) play an important regulatory role during adipogenesis, and have been studied extensively in this regard. Specifically, the switch between the differentiation of mesenchymal stem cells (MSCs) towards adipogenic vs. osteogenic lineages is regulated by miR‑204 which controls the expression of Runx2. However, the association between miR‑204-5p and the Wnt/β-catenin signaling pathway during adipogenesis has not yet been clarified. In the present study, we demonstrate that miR‑204-5p regulates the in vitro adipogenesis of human adipose-derived mesenchymal stem cells (hADSCs). The level of miR‑204-5p was shown to be gradually upregulated during adipocytic differentiation, together with the mRNA expression of the critical adipogenic transcription factors, cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), and the mature adipogenic marker, fatty acid binding protein 4 (FABP4). We further demonstrate that while the overexpression of miR‑204-5p promotes adipogenesis, its knockdown causes the inhibition of this process. We then used bioinformatics tools and luciferase reporter assay to establish that dishevelled segment polarity protein 3 (DVL3), a key regulator of the Wnt/β-catenin signaling pathway, is a direct target of miR‑204-5p. In addition, the overexpression of DVL3 led to an increase in β-catenin and cyclin D1 (CCND1) expression and, by contrast, the knockdown of DVL3 led to a decrease in the expression of β-catenin and CCND1. The knockdown of DVL3 significantly promoted adipogenesis. Finally, we demonstrated that the overexpression of miR‑204-5p induced the downregulation of β-catenin and the canonical Wnt target gene, CCND1, in mature adipoctyes, while its knockdown led to their upregulation. Taken together, our data suggest that miR‑204-5p regulates adipogenesis by controlling DVL3 expression and subsequently inhibiting the activation of the Wnt/β-catenin signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kanuri G and Bergheim I: In vitro and in vivo models of non-alcoholic fatty liver disease (NAFLD). Int J Mol Sci. 14:11963–11980. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Sung YY, Yoon T, Yang WK, Moon BC and Kim HK: Anti-obesity effects of Actinidia polygama extract in mice with high-fat diet-induced obesity. Mol Med Rep. 7:396–400. 2013.

3 

Ma J, Jiang Z, He S, Liu Y, Chen L, Long K, Jin L, Jiang A, Zhu L, Wang J, Li M and Li X: Intrinsic features in microRNA transcriptomes link porcine visceral rather than subcutaneous adipose tissues tometabolic risk. PLoS One. 8:e800412013. View Article : Google Scholar

4 

Song G, Xu G, Ji C, Shi C, Shen Y, Chen L, Zhu L, Yang L, Zhao Y and Guo X: The role of microRNA-26b in human adipocyte differentiation and proliferation. Gene. 10:481–487. 2014. View Article : Google Scholar

5 

Chen L, Song J, Cui J, Hou J, Zheng X, Li C and Liu L: microRNAs regulate adipocyte differentiation. Cell Biol Int. 37:533–546. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Karbiener M, Neuhold C, Oprriessnig P, Prokesch A, Bogner- Strauss JG and Scheideler M: MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2. RNA Biol. 8:850–860. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Wang Q, Li YC, Wang J, Kong J, Qi Y, Quigg RJ and Li X: miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci USA. 26:2889–2894. 2008. View Article : Google Scholar

8 

Lee EK, Lee MJ, Abdelmohsen K, Kim W, Kim MM, Srikantan S, Martindale JL, Hutchison ER, Kim HH, Marasa BS, Selimyan R, Egan JM, Smith SR, Fried SK and Gorospe M: miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Mol Cell Biol. 31:626–638. 2011. View Article : Google Scholar :

9 

Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, Lee YS and Kim JB: miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. Biochem Biophys Res Commun. 392:323–328. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Gerin I, Bommer GT, McCoin CS, Sousa KM, Krishnan V and MacDougald OA: Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis. Am J Physiol Endocrinol Metab. 299:E198–E206. 2010.PubMed/NCBI

11 

Martinelli R, Nardelli C, Pilone V, Buonomo T, Liguori R, Castanò I, Buono P, Masone S, Persico G, Forestieri P, Pastore L and Sacchetti L: miR-519d overexpression is associated with human obesity. Obesity (Silver Spring). 18:2170–2176. 2010. View Article : Google Scholar

12 

Kim YJ, Hwang SJ, Bae YC and Jung JS: MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stemcells derived from human adipose tissue. Stem Cells. 27:3093–3102. 2009.PubMed/NCBI

13 

Kennell JA, Gerin I, MacDougald OA and Cadigan KM: The microRNA miR-8 is a conserved negative regulator of Wnt signaling. Proc Natl Acad Sci USA. 105:15417–1522. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Chen H, Wang S, Chen L, Chen Y, Wu M, Zhang Y, Yu K, Huang Z, Qin L and Mo D: MicroRNA-344 inhibits 3T3-L1 cell differentiation via targeting GSK3β of Wnt/β-catenin signaling pathway. FEBS Lett. 588:429–435. 2013. View Article : Google Scholar

15 

Qin L, Chen Y, Niu Y, Chen W, Wang Q, Xiao S, Li A, Xie Y, Li J, Zhao X, He Z and Mo D: A deep investigation into the adipogenesis mechanism: profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/β-catenin signaling pathway. BMC Genomics. 11:3202010. View Article : Google Scholar

16 

Christodoulides C, Lagathu C, Sethi JK and Vidal-Puig A: Adipogenesis and WNT signaling. Trends Endocrinol Metab. 20:16–24. 2009. View Article : Google Scholar

17 

Huang J, Zhao L, Xing L and Chen D: MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 28:357–364. 2010.

18 

Yang X, Shang H, Katz A and Li X: A modified aggregate culture for chondrogenesis of human adipose-derived stem cells genetically modified with growth and differentiation factor 5. Biores Open Access. 2:258–265. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Hausman GJ, Dodson MV, Ajuwon K, Azain M, Barnes KM, Guan LL, Jiang Z, Poulors SP, Srainz RD, Smith S, Spurlock M, Novakofski J, Fernyhough ME and Bergen WG: Board-invited review: the biology and regulation of preadipocytes and adipocytes in meat animals. J Anim Sci. 87:1218–1246. 2009. View Article : Google Scholar

20 

Chartoumpekis DV, Zaravinos A, Ziros PG, Iskrenova RP, Psyrogiannis AI, Kyriazopoulou VE and Habeos IG: Differential expression of microRNAs in adipose tissue after long-term high-fat diet-induced obesity in mice. PLoS One. 7:e348722012. View Article : Google Scholar : PubMed/NCBI

21 

Fei J, Tamski H, Cook C and Santanam N: MicroRNA regulation of adipose derived stem cells in aging rats. PLoS One. 8:e592382013. View Article : Google Scholar : PubMed/NCBI

22 

Zhang Y, Xie RL, Gordon J, LeBlanc K, Stein JL, Lian JB, van Wijnen AJ and Stein GS: Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. J Biol Chem. 22:21926–21935. 2012. View Article : Google Scholar

23 

Liu J and Farmer SR: Regulating the balance between peroxi-some proliferator-activated receptor gamma andbeta-catenin signaling during adipogenesis. A glycogen synthase kinase 3beta phosphorylation-defective mutant of beta-catenin inhibits expression of a subset of adipogenic genes. J Biol Chem. 22:45020–45027. 2004. View Article : Google Scholar

24 

Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL and MacDougald OA: Inhibition of adipogenesis by Wnt signaling. Science. 11:950–953. 2000. View Article : Google Scholar

25 

Lee H, Kang R, Bae S and Yoon Y: AICAR, an activator of AMPK, inhibits adipogenesis via the WNT/β-catenin pathway in 3T3-L1 adipocytes. Int J Mol Med. 28:65–71. 2011.PubMed/NCBI

26 

Chan CY, Wei L, Castro-Muñozledo F and Koo WL: (−)-Epigallocatechin-3-gallate blocks 3T3-L1 adipose conversion by inhibition of cell proliferation and suppression of adipose phenotype expression. Life Sci. 21:779–785. 2011. View Article : Google Scholar

27 

Lee H, Bae S and Yoon Y: The anti-adipogenic effects of (−)epigallocatechin gallate are dependent on the WNT/β-catenin pathway. J Nutr Biochem. 24:1232–1240. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Lee H, Bae S, Kim YS and Yoon Y: WNT/β-catenin pathway mediates the anti-adipogenic effect of platycodin D, a natural compound found in Platycodon grandiflorum. Life Sci. 12:388–394. 2011. View Article : Google Scholar

29 

Lee H, Bae S and Yoon Y: Anti-adipogenic effects of 1,25-dihy-droxyvitamin D3 are mediated by the maintenance of the wingless-type MMTV integration site/β-catenin pathway. Int J Mol Med. 30:1219–1224. 2012.PubMed/NCBI

30 

Lagathu C, Christodoulides C, Virtue S, Cawthorn WP, Franzin C, Kimber WA, Nora ED, Campbell M, Medina- Gomez G, Cheyette BN, Vidal-Puig AJ and Sethi JK: Dact1, a nutritionally regulated preadipocyte gene, controls adipogen-esis by coordinating the Wnt/beta-catenin signaling network. Diabetes. 58:609–619. 2009. View Article : Google Scholar :

31 

Lee H, Kang R, Hahn Y, Yang Y, Kim SS, Cho SH, Chung SI and Yoon Y: Anti obesity effect of baicalin involves the modulations of proadipogenic and antiadipogenic regulators of the adipogenesis pathway. Phytother Res. 23:1615–1623. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
He H, Chen K, Wang F, Zhao L, Wan X, Wang L and Mo Z: miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling. Int J Mol Med 35: 1587-1595, 2015.
APA
He, H., Chen, K., Wang, F., Zhao, L., Wan, X., Wang, L., & Mo, Z. (2015). miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling. International Journal of Molecular Medicine, 35, 1587-1595. https://doi.org/10.3892/ijmm.2015.2160
MLA
He, H., Chen, K., Wang, F., Zhao, L., Wan, X., Wang, L., Mo, Z."miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling". International Journal of Molecular Medicine 35.6 (2015): 1587-1595.
Chicago
He, H., Chen, K., Wang, F., Zhao, L., Wan, X., Wang, L., Mo, Z."miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling". International Journal of Molecular Medicine 35, no. 6 (2015): 1587-1595. https://doi.org/10.3892/ijmm.2015.2160
Copy and paste a formatted citation
x
Spandidos Publications style
He H, Chen K, Wang F, Zhao L, Wan X, Wang L and Mo Z: miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling. Int J Mol Med 35: 1587-1595, 2015.
APA
He, H., Chen, K., Wang, F., Zhao, L., Wan, X., Wang, L., & Mo, Z. (2015). miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling. International Journal of Molecular Medicine, 35, 1587-1595. https://doi.org/10.3892/ijmm.2015.2160
MLA
He, H., Chen, K., Wang, F., Zhao, L., Wan, X., Wang, L., Mo, Z."miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling". International Journal of Molecular Medicine 35.6 (2015): 1587-1595.
Chicago
He, H., Chen, K., Wang, F., Zhao, L., Wan, X., Wang, L., Mo, Z."miR‑204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling". International Journal of Molecular Medicine 35, no. 6 (2015): 1587-1595. https://doi.org/10.3892/ijmm.2015.2160
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