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
January-2015 Volume 9 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
January-2015 Volume 9 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

Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy

  • Authors:
    • Yang‑Jun Li
    • Jie Zhang
    • Jing Han
    • Zhao‑Jiang Du
    • Ping Wang
    • Yong Guo
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Tangdu Hospital, The Fourth Military Medical University of the PLA, Xian, Shaanxi 710038, P.R. China
  • Pages: 89-97
    |
    Published online on: November 19, 2014
       https://doi.org/10.3892/etm.2014.2081
  • 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

This study used a streptozotocin (STZ)‑induced rat model of diabetes to investigate whether Ras‑related C3 botulinum toxin substrate 1 (Rac1) was involved in the pathogenesis of diabetic retinopathy. The effects of Rac1 inhibition on vascular endothelial (VE)‑cadherin and β‑catenin expression in high glucose‑induced rat retinal endothelial cells (RRECs) were additionally examined. Rac1 activation in the retinas from STZ‑induced diabetic rats and in high glucose‑induced RRECs was measured by reverse transcription‑quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. The expression levels of VE‑cadherin and β‑catenin were also examined with or without Rac1 inhibition through small interfering (si)RNA transfection. STZ‑induced diabetes was associated with an increase in the vascular permeability of the retina. Furthermore, Rac1 activation was increased in the retina of STZ‑induced diabetic rats and in high glucose‑induced RRECs compared with that in the controls. Immunohistochemistry showed that immunostaining of Rac1 was localized in the outer plexiform, inner nuclear, inner plexiform and ganglion cell layers and in the retinal microvasculature of rats. The expression of β‑catenin was increased in the retinas of the diabetic rats at four, eight and 12 weeks after the induction of diabetes compared with that in the controls. Additionally, Rac1 activation was required for the high glucose‑induced VE‑cadherin expression decrease and for β‑catenin expression in high glucose‑induced RRECs. Rac1 inhibition by Rac1‑siRNA transfection effectively prevented hyperpermeability, β‑catenin expression and the VE‑cadherin expression decrease in high glucose‑induced RRECs. In conclusion, diabetes affects the expression of Rac1 in the retina. Rac1 may be involved in the diabetes‑induced damage and/or alterations to the blood‑retinal barrier through changes in VE‑cadherin and β‑catenin expression.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Nelson WJ: Adaptation of core mechanisms to generate cell polarity. Nature. 422:766–774. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Corada M, Mariotti M, Thurston G, et al: Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci USA. 96:9815–9820. 1999. View Article : Google Scholar : PubMed/NCBI

3 

May C, Doody JF, Abdullah R, et al: Identification of a transiently exposed VE-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature. Blood. 105:4337–4344. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Weis WI and Nelson WJ: Re-solving the cadherin-catenin-actin conundrum. J Biol Chem. 281:35593–35597. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Potter MD, Barbero S and Cheresh DA: Tyrosine phosphorylation of VE-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state. J Biol Chem. 280:31906–31912. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Gumbiner BM: Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 6:622–634. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Hall A: Rho GTPases and the control of cell behaviour. Biochem Soc Trans. 33:891–895. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Ehrlich JS, Hansen MD and Nelson WJ: Spatio-temporal regulation of Rac1 localization and lamellipodia dynamics during epithelial cell-cell adhesion. Dev Cell. 3:259–270. 2002. View Article : Google Scholar : PubMed/NCBI

9 

van Wetering S, van Buul JD, Quik S, et al: Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells. J Cell Sci. 115:1837–1846. 2002.PubMed/NCBI

10 

Hage B, Meinel K, Baum I, Giehl K and Menke A: Rac1 activation inhibits E-cadherin-mediated adherens junctions via binding to IQGAP1 in pancreatic carcinoma cells. Cell Commun Signal. 7:232009. View Article : Google Scholar : PubMed/NCBI

11 

Monaghan-Benson E and Burridge K: The regulation of vascular endothelial growth factor-induced microvascular permeability requires Rac and reactive oxygen species. J Biol Chem. 284:25602–25611. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Wu X, Tu X, Joeng KS, et al: Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell. 133:340–353. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Xu Q, Qaum T and Adamis AP: Sensitive blood-retinal barrier breakdown quantitation using Evans blue. Invest Ophthalmol Vis Sci. 42:789–794. 2001.PubMed/NCBI

14 

Gao G, Shao C, Zhang SX, et al: Kallikrein-binding protein inhibits retinal neovascularization and decreases vascular leakage. Diabetologia. 46:689–698. 2003.PubMed/NCBI

15 

Boeri D, Cagliero E, Podestá F and Lorenzi M: Vascular wall von Willebrand factor in human diabetic retinopathy. Invest Ophthalmol Vis Sci. 35:600–607. 1994.PubMed/NCBI

16 

Lecomte M, Paget C, Ruggiero D, Wiernsperger N and Lagarde M: Docosahexaenoic acid is a major n-3 polyunsaturated fatty acid in bovine retinal microvessels. J Neurochem. 66:2160–2167. 1996. View Article : Google Scholar : PubMed/NCBI

17 

Elbashir SM, Harborth J, Lendeckel W, et al: Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 411:494–498. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Kim JH, Kim JH, Jun HO, Yu YS and Kim KW: Inhibition of protein kinase C delta attenuates blood-retinal barrier breakdown in diabetic retinopathy. Am J Pathol. 176:1517–1524. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Sander EE, van Delft S, ten Klooster JP, et al: Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J Cell Biol. 143:1385–1398. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Do carmo A, Ramos P, Reis A, Proença R and Cunha-vaz JG: Breakdown of the inner and outer blood retinal barrier in streptozotocin-induced diabetes. Exp Eye Res. 67:569–575. 1998. View Article : Google Scholar

21 

Moldovan L, Moldovan NI, Sohn RH, Parikh SA and Goldschmidt-Clermont PJ: Redox changes of cultured endothelial cells and actin dynamics. Circ Res. 86:549–557. 2000. View Article : Google Scholar : PubMed/NCBI

22 

Peterson LJ, Wittchen ES, Geisen P, Burridge K and Hartnett ME: Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1. Exp Eye Res. 84:737–744. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Wójciak-Stothard B, Potempa S, Eichholtz T and Ridley AJ: Rho and Rac but not Cdc42 regulate endothelial cell permeability. J Cell Sci. 114:1343–1355. 2001.PubMed/NCBI

24 

Braga VM, Del Maschio A, Machesky L and Dejana E: Regulation of cadherin function by Rho and Rac: modulation by junction maturation and cellular context. Mol Biol Cell. 10:9–22. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Gavard J and Gutkind JS: VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol. 8:1223–1234. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Stockton RA, Schaefer E and Schwartz MA: p21-activated kinase regulates endothelial permeability through modulation of contractility. J Biol Chem. 279:46621–46630. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Zhang XZ, Huang X, Qiao JH, Zhang JJ and Zhang MX: Inhibition of hypoxia-induced retinal neovascularization in mice with short hairpin RNA targeting Rac1, possibly via blockading redox signaling. Exp Eye Res. 92:473–481. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Navaratna D, McGuire PG, Menicucci G and Das A: Proteolytic degradation of VE-cadherin alters the blood-retinal barrier in diabetes. Diabetes. 56:2380–2387. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Chen Y, Hu Y, Zhou T, et al: Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models. Am J Pathol. 175:2676–2685. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li YJ, Zhang J, Han J, Du ZJ, Wang P and Guo Y: Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy. Exp Ther Med 9: 89-97, 2015.
APA
Li, Y., Zhang, J., Han, J., Du, Z., Wang, P., & Guo, Y. (2015). Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy. Experimental and Therapeutic Medicine, 9, 89-97. https://doi.org/10.3892/etm.2014.2081
MLA
Li, Y., Zhang, J., Han, J., Du, Z., Wang, P., Guo, Y."Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy". Experimental and Therapeutic Medicine 9.1 (2015): 89-97.
Chicago
Li, Y., Zhang, J., Han, J., Du, Z., Wang, P., Guo, Y."Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy". Experimental and Therapeutic Medicine 9, no. 1 (2015): 89-97. https://doi.org/10.3892/etm.2014.2081
Copy and paste a formatted citation
x
Spandidos Publications style
Li YJ, Zhang J, Han J, Du ZJ, Wang P and Guo Y: Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy. Exp Ther Med 9: 89-97, 2015.
APA
Li, Y., Zhang, J., Han, J., Du, Z., Wang, P., & Guo, Y. (2015). Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy. Experimental and Therapeutic Medicine, 9, 89-97. https://doi.org/10.3892/etm.2014.2081
MLA
Li, Y., Zhang, J., Han, J., Du, Z., Wang, P., Guo, Y."Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy". Experimental and Therapeutic Medicine 9.1 (2015): 89-97.
Chicago
Li, Y., Zhang, J., Han, J., Du, Z., Wang, P., Guo, Y."Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy". Experimental and Therapeutic Medicine 9, no. 1 (2015): 89-97. https://doi.org/10.3892/etm.2014.2081
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