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
July-2018 Volume 42 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-2018 Volume 42 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

miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway

  • Authors:
    • Hongtao Hu
    • Shuang Hu
    • Shen Xu
    • Yue Gao
    • Fang Zeng
    • Hua Shui
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
  • Pages: 453-460
    |
    Published online on: March 22, 2018
       https://doi.org/10.3892/ijmm.2018.3579
  • 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

Renal interstitial fibrosis is a necessary step in the progression of chronic kidney to end stage renal disease. MicroRNA-29 (miR-29) has been shown to play essential roles in epithelial-mesenchymal transition (EMT), and thus may contribute to the regulation of renal interstitial fibrosis. However, the role of miR-29 in the regulation of EMT during chronic kidney disease and renal transplantation has been a source of intense debate, and the mechanisms underlying this process are incompletely understood. In this study, we investigated the function of miR-29b in the regulation of EMT and to gain a better understanding of the mechanism by which miR-29b modulates EMT by targeting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway during the process of renal interstitial fibrosis. The rat proximal tubular epithelial cell line NRK-52E was cultured in DMEM and treated with angiotensin II (Ang II) at various concentrations. RT-PCR was performed to investigate changes in the levels of expression of miR-29b in NRK-52E cells and western blotting was used to analyze the expression of PI3K, p-AKT, vimentin and keratin 18. The result of the study show that treatment of NRK-52E cells with Ang II induced the transition of the cellular phenotype from epithelial to mesenchymal and upregulated the PI3K/AKT signaling pathway; this was also found following treatment with a phosphatase and tensin homolog on chromosome 10 (PTEN)-specific inhibitor. Increased expression of miR-29b was able to reverse the phenotype induced by Ang II in NRK-52E cells and blocking miR-29b activity with an miR-29b inhibitor resulted in enhanced EMT. Additionally, the PI3K/AKT signaling pathway was found to be suppressed in the presence of enhanced expression of miR-29b by direct binding to 3'-untranslated region (3'-UTR) of PIK3R2. We concluded that miR-29b plays an important role in the negative regulation of Ang II-induced EMT via PI3K/AKT signaling pathway and propose that enhancing miR-29b level or blocking PI3K/AKT signaling pathway may be a novel therapeutic target in renal interstitial fibrosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Ballhause TM, Soldati R and Mertens PR: Sources of myofibroblasts in kidney fibrosis: All answers are correct, however to different extent! Int Urol Nephrol. 46:659–664. 2014. View Article : Google Scholar

2 

Liu Y: New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol. 21:212–222. 2010. View Article : Google Scholar

3 

Cantrell DA: Phosphoinositide 3-kinase signalling pathways. J Cell Sci. 114:1439–1445. 2001.PubMed/NCBI

4 

Ye B, Jiang LL, Xu HT, Zhou DW and Li ZS: Expression of PI3K/AKT pathway in gastric cancer and its blockade suppresses tumor growth and metastasis. Int J Immunopathol Pharmacol. 25:627–636. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Hassan B, Akcakanat A, Holder AM and Meric-Bernstam F: Targeting the PI3-kinase/Akt/mTOR signaling pathway. Surg Oncol Clin N Am. 22:641–664. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Yang T, Liang Y, Lin Q, Liu J, Luo F, Li X, Zhou H, Zhuang S and Zhang H: miR-29 mediates TGFβ1-induced extracellular matrix synthesis through activation of PI3K-AKT pathway in human lung fibroblasts. J Cell Biochem. 114:1336–1342. 2013. View Article : Google Scholar

7 

Wang J, Chu ES, Chen HY, Man K, Go MY, Huang XR, Lan HY, Sung JJ and Yu J: microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway. Oncotarget. 6:7325–7338. 2015.

8 

Qin J, Xie YY, Huang L, Yuan QJ, Mei WJ, Yuan XN, Hu GY, Cheng GJ, Tao LJ and Peng ZZ: Fluorofenidone inhibits nicotinamide adenine dinucleotide phosphate oxidase via PI3K/Akt pathway in the pathogenesis of renal interstitial fibrosis. Nephrology (Carlton). 18:690–699. 2013.

9 

Burns WC, Velkoska E, Dean R, Burrell LM and Thomas MC: Angiotensin II mediates epithelial-to-mesenchymal transformation in tubular cells by ANG 1-7/MAS-1-dependent pathways. Am J Physiol Renal Physiol. 299:F585–F593. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Yan B, Guo Q, Fu FJ, Wang Z, Yin Z, Wei YB and Yang JR: The role of miR-29b in cancer: Regulation, function, and signaling. Onco Targets Ther. 8:539–548. 2015.PubMed/NCBI

11 

Bayoumi AS, Sayed A, Broskova Z, Teoh JP, Wilson J, Su H, Tang YL and Kim IM: Crosstalk between long noncoding RNAs and microRNAs in health and disease. Int J Mol Sci. 17:E3562016. View Article : Google Scholar : PubMed/NCBI

12 

van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA and Olson EN: Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA. 105:13027–13032. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Cushing L, Kuang PP, Qian J, Shao F, Wu J, Little F, Thannickal VJ, Cardoso WV and Lü J: miR-29 is a major regulator of genes associated with pulmonary fibrosis. Am J Respir Cell Mol Biol. 45:287–294. 2011. View Article : Google Scholar :

14 

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

15 

Pan J, Zhang J, Zhang X, Zhou X, Lu S, Huang X, Shao J, Lou G, Yang D and Geng YJ: Role of microRNA-29b in angiotensin II-induced epithelial-mesenchymal transition in renal tubular epithelial cells. Int J Mol Med. 34:1381–1387. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Okada H, Ban S, Nagao S, Takahashi H, Suzuki H and Neilson EG: Progressive renal fibrosis in murine polycystic kidney disease: An immunohistochemical observation. Kidney Int. 58:587–597. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Djudjaj S, Papasotiriou M, Bülow RD, Wagnerova A, Lindenmeyer MT, Cohen CD, Strnad P, Goumenos DS, Floege J and Boor P: Keratins are novel markers of renal epithelial cell injury. Kidney Int. 89:792–808. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Chen J, Chen JK and Harris RC: Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway. Mol Cell Biol. 32:981–991. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Burns WC and Thomas MC: Angiotensin II and its role in tubular epithelial to mesenchymal transition associated with chronic kidney disease. Cells Tissues Organs. 193:74–84. 2011. View Article : Google Scholar

20 

Yano N, Suzuki D, Endoh M, Zhao TC, Padbury JF and Tseng YT: A novel phosphoinositide 3-kinase-dependent pathway for angiotensin II/AT-1 receptor-mediated induction of collagen synthesis in MES-13 mesangial cells. J Biol Chem. 282:18819–18830. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Macconi D, Remuzzi G and Benigni A: Key fibrogenic mediators: Old players. Renin-angiotensin system. Kidney Int Suppl (2011). 4:58–64. 2014. View Article : Google Scholar

22 

Zavadil J and Böttinger EP: TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 24:5764–5774. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Yang F, Huang XR, Chung AC, Hou CC, Lai KN and Lan HY: Essential role for Smad3 in angiotensin II-induced tubular epithelial-mesenchymal transition. J Pathol. 221:390–401. 2010.PubMed/NCBI

24 

Meng XM, Tang PM, Li J and Lan HY: TGF-β/Smad signaling in renal fibrosis. Front Physiol. 6:822015. View Article : Google Scholar

25 

Rodríguez-Vita J, Sánchez-López E, Esteban V, Rupérez M, Egido J and Ruiz-Ortega M: Angiotensin II activates the Smad pathway in vascular smooth muscle cells by a transforming growth factor-beta-independent mechanism. Circulation. 111:2509–2517. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Denby L and Baker AH: Targeting non-coding RNA for the therapy of renal disease. Curr Opin Pharmacol. 27:70–77. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Simpson K, Wonnacott A, Fraser DJ and Bowen T: MicroRNAs in diabetic nephropathy: From biomarkers to therapy. Curr Diab Rep. 16:352016. View Article : Google Scholar : PubMed/NCBI

28 

Gomez IG, Nakagawa N and Duffield JS: MicroRNAs as novel therapeutic targets to treat kidney injury and fibrosis. Am J Physiol Renal Physiol. 310:F931–F944. PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Hu H, Hu S, Xu S, Gao Y, Zeng F and Shui H: miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway. Int J Mol Med 42: 453-460, 2018.
APA
Hu, H., Hu, S., Xu, S., Gao, Y., Zeng, F., & Shui, H. (2018). miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway. International Journal of Molecular Medicine, 42, 453-460. https://doi.org/10.3892/ijmm.2018.3579
MLA
Hu, H., Hu, S., Xu, S., Gao, Y., Zeng, F., Shui, H."miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway". International Journal of Molecular Medicine 42.1 (2018): 453-460.
Chicago
Hu, H., Hu, S., Xu, S., Gao, Y., Zeng, F., Shui, H."miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway". International Journal of Molecular Medicine 42, no. 1 (2018): 453-460. https://doi.org/10.3892/ijmm.2018.3579
Copy and paste a formatted citation
x
Spandidos Publications style
Hu H, Hu S, Xu S, Gao Y, Zeng F and Shui H: miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway. Int J Mol Med 42: 453-460, 2018.
APA
Hu, H., Hu, S., Xu, S., Gao, Y., Zeng, F., & Shui, H. (2018). miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway. International Journal of Molecular Medicine, 42, 453-460. https://doi.org/10.3892/ijmm.2018.3579
MLA
Hu, H., Hu, S., Xu, S., Gao, Y., Zeng, F., Shui, H."miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway". International Journal of Molecular Medicine 42.1 (2018): 453-460.
Chicago
Hu, H., Hu, S., Xu, S., Gao, Y., Zeng, F., Shui, H."miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway". International Journal of Molecular Medicine 42, no. 1 (2018): 453-460. https://doi.org/10.3892/ijmm.2018.3579
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