Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Extracellular matrix alterations after blood instillation in tunica albuginea of rats

International Journal of Impotence Research volume 30, pages 85–92 (2018)Cite this article

Subjects

Abstract

The cause of Peyronie’s disease (PD) is still not completely understood. The objective of this study, therefore, was to analyze the histological and biochemical alterations that occur after the instillation of blood in the tunica albuginea (TA) of rats with an emphasis on the remodeling process of ECM. Thirty male Wistar rats were divided into 4 groups: two control groups with instillation of distilled water in TA followed by penectomy after 15 days or 45 days, respectively and two experimental groups with instillation of blood in TA followed by penectomy after 15 days or 45 days, respectively. Histological, immunofluorescent and immunohistochemical analyses were performed. The higher presence of fibrotic tissue in rats injected with blood demonstrated alterations in TA similar to inflammation found in PD. The increased expression of TGF-β, MMP9, HPSE, and biglycan associated with the decreased expression of syndecan-1 and aggrecan in the experimental groups suggested an enhancement in the remodeling of ECM. The results contribute to show that blood instillation on TA appears to trigger alterations in the ECM similar to the ones found in inflammatory diseases such as PD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Sommer F, Schwarzer U, Wassmer G, Bloch W, Braun M, Klotz T, et al. Epidemiology of Peyronie’s disease. Int J Impot Res. 2002;14:379–83.

    Article  CAS  PubMed  Google Scholar 

  2. Gokce A, Abd Elmageed ZY, Lasker GF, Bouljihad M, Braun SE, Kim H, et al. Intratunical injection of genetically modified adipose tissue-derived stem cells with human interferon alpha-2b for treatment of erectile dysfunction in a rat model of tunica albugineal fibrosis. J Sex Med. 2015;12:1533–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kwon KD, Choi MJ, Park JM, Song KM, Kwon MH, Batbold D, et al. Silencing histone deacetylase 2 using small hairpin RNA induces regression of fibrotic plaque in a rat model of Peyronie’s disease. BJU Int. 2014;114:926–36.

    Article  CAS  PubMed  Google Scholar 

  4. Gelbard MK, Dorey F, James K. The natural history of Peyronie’s disease. J Urol. 1990;144:1376–9.

    Article  CAS  PubMed  Google Scholar 

  5. Nelson CJ, Mulhall JP. Psychological impact of Peyronie’s disease: a review. J Sex Med. 2013;10:653–60.

    Article  PubMed  Google Scholar 

  6. Chung E, Ralph D, Kagioglu A, Garaffa G, Shamsodini A, Bivalacqua T, et al. Evidence-based management guidelines on Peyronie’s disease. J Sex Med. 2016;13:905–23.

    Article  PubMed  Google Scholar 

  7. Ralph D, Gonzalez-Cadavid N, Mirone V, Perovic S, Sohn M, Usta M, et al. The management of Peyronie’s disease: evidence-based 2010 guidelines. J Sex Med. 2010;7:2359–74.

    Article  PubMed  Google Scholar 

  8. Gonzalez-Cadavid NF, Rajfer J. Mechanisms of disease: new insights into the cellular and molecular pathology of Peyronie’s disease. Nat Clin Pract Urol. 2005;2:291–7.

    Article  CAS  PubMed  Google Scholar 

  9. Chung E, De Young L, Brock GB. Rat as an animal model for Peyronie’s disease research: a review of current methods and the peer-reviewed literature. Int J Impot Res. 2011;23:235–41.

    Article  CAS  PubMed  Google Scholar 

  10. Badalamente MA, Hurst LC. The biochemistry of Dupuytren’s disease. Hand Clin. 1999;15:35–42. v-vi.

    CAS  PubMed  Google Scholar 

  11. Matos LL, Stabenow E, Tavares MR, Ferraz AR, Capelozzi VL, Pinhal MA. Immunohistochemistry quantification by a digital computer-assisted method compared to semiquantitative analysis. Clin (Sao Paulo). 2006;61:417–24.

    Article  Google Scholar 

  12. Charan J, Kantharia ND. How to calculate sample size in animal studies? J Pharmacol Pharmacother. 2013;4:303–6.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ahuja SK, Sikka SC, Hellstrom WJ. Stimulation of collagen production in an in vitro model for Peyronie’s disease. Int J Impot Res. 1999;11:207–12.

    Article  CAS  PubMed  Google Scholar 

  14. Qian A, Meals RA, Rajfer J, Gonzalez-Cadavid NF. Comparison of gene expression profiles between Peyronie’s disease and Dupuytren’s contracture. Urology. 2004;64:399–404.

    Article  CAS  PubMed  Google Scholar 

  15. Ratajczak-Wielgomas K, Gosk J, Rabczynski J, Augoff K, Podhorska-Okolow M, Gamian A, et al. Expression of MMP-2, TIMP-2, TGF-beta1, and decorin in Dupuytren’s contracture. Connect Tissue Res. 2012;53:469–77.

    Article  CAS  PubMed  Google Scholar 

  16. Jarvelainen H, Sainio A, Koulu M, Wight TN, Penttinen R. Extracellular matrix molecules: potential targets in pharmacotherapy. Pharmacol Rev. 2009;61:198–223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Neely AN, Clendening CE, Gardner J, Greenhalgh DG, Warden GD. Gelatinase activity in keloids and hypertrophic scars. Wound Repair Regen. 1999;7:166–71.

    Article  CAS  PubMed  Google Scholar 

  18. Arthur MJ. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2000;279:G245–9.

    Article  CAS  PubMed  Google Scholar 

  19. Eckes B, Zigrino P, Kessler D, Holtkotter O, Shephard P, Mauch C, et al. Fibroblast-matrix interactions in wound healing and fibrosis. Matrix Biol. 2000;19:325–32.

    Article  CAS  PubMed  Google Scholar 

  20. Ulrich D, Hrynyschyn K, Pallua N. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in sera and tissue of patients with Dupuytren’s disease. Plast Reconstr Surg. 2003;112:1279–86.

    Article  PubMed  Google Scholar 

  21. McKenzie EA. Heparanase: a target for drug discovery in cancer and inflammation. Br J Pharmacol. 2007;151:1–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dudas J, Kovalszky I, Gallai M, Nagy JO, Schaff Z, Knittel T, et al. Expression of decorin, transforming growth factor-beta 1, tissue inhibitor metalloproteinase 1 and 2, and type IV collagenases in chronic hepatitis. Am J Clin Pathol. 2001;115:725–35.

    Article  CAS  PubMed  Google Scholar 

  23. Beanes SR, Dang C, Soo C, Wang Y, Urata M, Ting K, et al. Down-regulation of decorin, a transforming growth factor-beta modulator, is associated with scarless fetal wound healing. J Pediatr Surg. 2001;36:1666–71.

    Article  CAS  PubMed  Google Scholar 

  24. Imai K, Hiramatsu A, Fukushima D, Pierschbacher MD, Okada Y. Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release. Biochem J. 1997;322:809–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kozma EM, Olczyk K, Wisowski G, Glowacki A, Bobinski R. Alterations in the extracellular matrix proteoglycan profile in Dupuytren’s contracture affect the palmar fascia. J Biochem. 2005;137:463–76.

    Article  CAS  PubMed  Google Scholar 

  26. Kozma EM, Glowacki A, Olczyk K, Ciecierska M. Dermatan sulfate remodeling associated with advanced Dupuytren’s contracture. Acta Biochim Pol. 2007;54:821–30.

    CAS  PubMed  Google Scholar 

  27. Lopez-Casillas F, Payne HM. Andres IVEotEMCA, Collagen Types I and II by Articular Cartilage-Derived Chondrocytes.J. L., Massague J. Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites. J Cell Biol. 1994;124:557–68.

    Article  CAS  PubMed  Google Scholar 

  28. Zavadil J, Bitzer M, Liang D, Yang YC, Massimi A, Kneitz S, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci USA. 2001;98:6686–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schneevoigt J, Fabian C, Leovsky C, Seeger J, Bahramsoltani M. In vitro expression of the extracellular matrix components aggrecan, collagen types I and II by articular cartilage-derived chondrocytes. Anat Histol Embryol. 2017;46(1):43-50.

Download references

Acknowledgements

This work received financial support from FAPESP (São Paulo Research Foundation), CNPq (National Counsel of Technological and Scientific Development) and CAPES (Staff Development Committee of Higher Education).

Author information

Authors and Affiliations

  1. Faculdade de Medicina do ABC, Urology Department, Santo André, Brazil

    David J. Cohen

  2. Faculdade de Medicina ABC, Urology Department, Santo André, Brazil

    André V. Oliveira

  3. Faculdade de Medicina ABC, Biochemistry Department, Santo André, Brazil

    Théresè R. Theodoro

  4. Faculdade de Medicina ABC, Animal House Facility, São Paulo, Brazil

    Giuliana Petri

  5. Faculdade de Medicina ABC, Biochemistry Department, Santo André, Brazil

    Carina M. Melo

  6. Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil

    Carina M. Melo

  7. Faculdade de Medicina ABC, Biochemistry Department, Santo André, Brazil

    Renan P. Cavalheiro

  8. Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil

    Renan P. Cavalheiro

  9. Biochemistry Department, Universidade Federal do ABC, São Paulo, Brazil

    Helena B. Nader

  10. Faculdade de Medicina ABC, Pathology Department, Santo André, Brazil

    Ana M. Mader

  11. Faculdade de Medicina ABC, Biochemistry Department, Santo André, Brazil

    Maria A. S. Pinhal

  12. Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil

    Maria A. S. Pinhal

  13. Faculdade de Medicina ABC, Urology Department, Santo André, Brazil

    Sidney Glina

Authors
  1. David J. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. André V. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Théresè R. Theodoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuliana Petri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carina M. Melo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Renan P. Cavalheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Helena B. Nader
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ana M. Mader
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maria A. S. Pinhal
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sidney Glina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sidney Glina.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cohen, D.J., Oliveira, A.V., Theodoro, T.R. et al. Extracellular matrix alterations after blood instillation in tunica albuginea of rats. Int J Impot Res 30, 85–92 (2018). https://doi.org/10.1038/s41443-017-0015-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41443-017-0015-1

This article is cited by

Search

Advanced search

Quick links