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
May-2017 Volume 39 Issue 5

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
May-2017 Volume 39 Issue 5

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

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

  • Authors:
    • Yunzhuo Ren
    • Chunyang Du
    • Yonghong Shi
    • Jingying Wei
    • Haijiang Wu
    • Huixian Cui
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Anatomy, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
  • Pages: 1317-1324
    |
    Published online on: March 22, 2017
       https://doi.org/10.3892/ijmm.2017.2931
  • 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 transforming growth factor-β1 (TGF-β1)/connective tissue growth factor (CTGF) pathway plays an important role in the pathogenesis and progression of chronic kidney disease. Oxidative stress is also involved in TGF-β1 signalling. Sirtuin 1 (Sirt1) exerts a number of pleiotropic effects, protecting against renal disease, including inhibiting fibrosis and oxidative metabolism. In this study, we investigated the role of the Sirt1 activator, SRT1720, in unilateral ureteral obstruction (UUO)-induced tubulointerstitial fibrosis and aimed to determine whether this role depends on the inhibition of oxidative stress and the TGF-β1/CTGF pathway. Renal fibrosis was induced by UUO in CD1 mice. SRT1720 (100 mg/kg) was administered by intraperitoneal injection for 3 days prior to UUO and this was continued for 7 days following UUO. Histological changes were examined by Masson's trichrome staining. The expression of fibrosis-related factors was evaluated by immunohistochemistry, western blot analysis and RT-qPCR. Apoptosis was also examined. We also examined the superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels. UUO induced renal fibrosis and apoptosis and decreased Sirt1 expression. The administration of SRT1720 increased the Sirt1 levels and partially attenuated UUO-induced renal fibrosis and apoptosis. Furthermore, SRT1720 attenuated the levels of oxidative stress (it decreased the MDA levels, and increased the SOD, GPx and GSH levels), which suggests that it protected the cells against ROS-induced damage. Moreover, SRT1720 effectively inhibited the levels of TGF-β1/CTGF induced by UUO. On the whole, these findings indicate that the Sirt1 activator, SRT1720, exerts protective effects against UUO-induced tubulointerstitial fibrosis. The mechanisms of action of SRT1720 may include, at least in part, the suppression of renal oxidative stress and the TGF-β1/CTGF signalling pathway. The Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Klahr S and Morrissey J: Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol. 283:F861–F875. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Leask A and Abraham DJ: TGF-beta signaling and the fibrotic response. FASEB J. 18:816–827. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Devarajan P: Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 17:1503–1520. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Chiu C, Maddock DA, Zhang Q, Souza KP, Townsend AR and Wan Y: TGF-beta-induced p38 activation is mediated by Rac1-regulated generation of reactive oxygen species in cultured human keratinocytes. Int J Mol Med. 8:251–255. 2001.PubMed/NCBI

5 

Herrera B, Alvarez AM, Sánchez A, Fernández M, Roncero C, Benito M and Fabregat I: Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor (β) in fetal hepatocytes. FASEB J. 15:741–751. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Michan S and Sinclair D: Sirtuins in mammals: Insights into their biological function. Biochem J. 404:1–13. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Kim DH, Jung YJ, Lee JE, Lee AS, Kang KP, Lee S, Park SK, Han MK, Lee SY, Ramkumar KM, et al: SIRT1 activation by resveratrol ameliorates cisplatin-induced renal injury through deacetylation of p53. Am J Physiol Renal Physiol. 301:F427–F435. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Huang XZ, Wen D, Zhang M, Xie Q, Ma L, Guan Y, Ren Y, Chen J and Hao CM: Sirt1 activation ameliorates renal fibrosis by inhibiting the TGF-β/Smad3 pathway. J Cell Biochem. 115:996–1005. 2014. View Article : Google Scholar

9 

Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isshiki K, Isono M, Uzu T, Guarente L, Kashiwagi A, et al: SIRT1 inhibits transforming growth factor beta-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation. J Biol Chem. 282:151–158. 2007. View Article : Google Scholar

10 

Mao B, Hu F, Cheng J, Wang P, Xu M, Yuan F, Meng S, Wang Y, Yuan Z and Bi W: SIRT1 regulates YAP2-mediated cell proliferation and chemoresistance in hepatocellular carcinoma. Oncogene. 33:1468–1474. 2014. View Article : Google Scholar

11 

Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, et al: Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 450:712–716. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Gano LB, Donato AJ, Pasha HM, Hearon CM Jr, Sindler AL and Seals DR: The SIRT1 activator SRT1720 reverses vascular endothelial dysfunction, excessive superoxide production, and inflammation with aging in mice. Am J Physiol Heart Circ Physiol. 307:H1754–H1763. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Shimizu H, Maruyama S, Yuzawa Y, Kato T, Miki Y, Suzuki S, Sato W, Morita Y, Maruyama H, Egashira K, et al: Antimonocyte chemoattractant protein-1 gene therapy attenuated renal injury induced by protein-overload proteinuria. J Am Soc Nephrol. 14:1496–1505. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔC(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

15 

Duymelinck C, Deng JT, Dauwe SE, De Broe ME and Verpooten GA: Inhibition of the matrix metalloproteinase system in a rat model of chronic cyclosporine nephropathy. Kidney Int. 54:804–818. 1998. View Article : Google Scholar : PubMed/NCBI

16 

Yang J and Liu Y: Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am J Pathol. 159:1465–1475. 2001. View Article : Google Scholar : PubMed/NCBI

17 

He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, Yang HC, Fogo AB, Zent R, Harris RC, et al: Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest. 120:1056–1068. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isono M, Isshiki K, Uzu T, Kashiwagi A and Koya D: Silent information regulator 2 (SIRT1) attenuates oxidative stress-induced mesangial cell apoptosis via p53 deacetylation. Free Radic Biol Med. 40:2175–2182. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Chuang PY, Dai Y, Liu R, He H, Kretzler M, Jim B, Cohen CD and He JC: Alteration of forkhead box O (foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus. PLoS One. 6:e235662011. View Article : Google Scholar : PubMed/NCBI

20 

Liu Y: Cellular and molecular mechanisms of renal fibrosis. Nat Rev Nephrol. 7:684–696. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Franklin TJ: Therapeutic approaches to organ fibrosis. Int J Biochem Cell Biol. 29:79–89. 1997. View Article : Google Scholar : PubMed/NCBI

22 

Sánchez-López E, Rodrigues Díez R, Rodríguez Vita J, Rayego Mateos S, Rodrigues Díez RR, Rodríguez García E, Lavoz Barria C, Mezzano S, Egido J, Ortiz A, Ruiz-Ortega M and Selgas R: Connective tissue growth factor (CTGF): a key factor in the onset and progression of kidney damage. Nefrologia. 29:382–391. 2009.In Spanish.

23 

Border WA and Noble NA: Transforming growth factor beta in tissue fibrosis. N Engl J Med. 331:1286–1292. 1994. View Article : Google Scholar : PubMed/NCBI

24 

Ito Y, Aten J, Bende RJ, Oemar BS, Rabelink TJ, Weening JJ and Goldschmeding R: Expression of connective tissue growth factor in human renal fibrosis. Kidney Int. 53:853–861. 1998. View Article : Google Scholar : PubMed/NCBI

25 

Yokoi H, Sugawara A, Mukoyama M, Mori K, Makino H, Suganami T, Nagae T, Yahata K, Fujinaga Y, Tanaka I, et al: Role of connective tissue growth factor in profibrotic action of transforming growth factor-beta: A potential target for preventing renal fibrosis. Am J Kidney Dis. 38(Suppl 1): S134–S138. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Modi KS, Morrissey J, Shah SV, Schreiner GF and Klahr S: Effects of probucol on renal function in rats with bilateral ureteral obstruction. Kidney Int. 38:843–850. 1990. View Article : Google Scholar : PubMed/NCBI

27 

Sunami R, Sugiyama H, Wang DH, Kobayashi M, Maeshima Y, Yamasaki Y, Masuoka N, Ogawa N, Kira S and Makino H: Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and exacerbates renal fibrosis after unilateral ureteral obstruction. Am J Physiol Renal Physiol. 286:F1030–F1038. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ren Y, Du C, Shi Y, Wei J, Wu H and Cui H: The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress. Int J Mol Med 39: 1317-1324, 2017.
APA
Ren, Y., Du, C., Shi, Y., Wei, J., Wu, H., & Cui, H. (2017). The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress. International Journal of Molecular Medicine, 39, 1317-1324. https://doi.org/10.3892/ijmm.2017.2931
MLA
Ren, Y., Du, C., Shi, Y., Wei, J., Wu, H., Cui, H."The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress". International Journal of Molecular Medicine 39.5 (2017): 1317-1324.
Chicago
Ren, Y., Du, C., Shi, Y., Wei, J., Wu, H., Cui, H."The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress". International Journal of Molecular Medicine 39, no. 5 (2017): 1317-1324. https://doi.org/10.3892/ijmm.2017.2931
Copy and paste a formatted citation
x
Spandidos Publications style
Ren Y, Du C, Shi Y, Wei J, Wu H and Cui H: The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress. Int J Mol Med 39: 1317-1324, 2017.
APA
Ren, Y., Du, C., Shi, Y., Wei, J., Wu, H., & Cui, H. (2017). The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress. International Journal of Molecular Medicine, 39, 1317-1324. https://doi.org/10.3892/ijmm.2017.2931
MLA
Ren, Y., Du, C., Shi, Y., Wei, J., Wu, H., Cui, H."The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress". International Journal of Molecular Medicine 39.5 (2017): 1317-1324.
Chicago
Ren, Y., Du, C., Shi, Y., Wei, J., Wu, H., Cui, H."The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress". International Journal of Molecular Medicine 39, no. 5 (2017): 1317-1324. https://doi.org/10.3892/ijmm.2017.2931
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