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.

  • Original Article
  • Published:

Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction

Abstract

Phenotypic modulation from a contractile to a proliferative state within vascular smooth muscle cells has a critical role in the pathogenesis of a variety of cardiovascular diseases. To investigate the characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction, a group of Sprague–Dawley rats (n=30) were induced by intraperitoneal injection of streptozotocin (60 mg kg−1) and screened by subcutaneous injection of apomorphine (100 μg kg−1) for the measurement and comparison of the penile erections, and then three different groups were defined. Primary corpus cavernosum smooth muscle cells were cultured and passaged. The cavernous tissue segments were subjected to quantitative real-time polymerase chain reaction to determine the expressions of smooth muscle α-actin (SMA), SM myosin heavy chain (SMMHC), smoothelin, calponin and myocardin. Cell contractility in vitro and western blot analysis of SMA and SMMHC in the cavernous tissues and cells were determined. Compared with the control group (n=8) and the diabetes mellitus group (n=5), the expressions of SMA, calponin, SMMHC, smoothelin and myocardin mRNA were decreased in the cavernous tissues in rats of the diabetic erectile dysfunction group (n=15; P=0.001 and 0.02, P=0.014 and 0.012, both P<0.001, P=0.005 and <0.001, P=0.003 and 0.035, respectively). The levels of SMA and SMMHC proteins showed a significant decrease in cavernous tissues and cultured cells in rats of the diabetic erectile dysfunction group. Cells of the diabetic erectile dysfunction group exhibited significantly less contractility compared with those of other groups (P<0.001). Corpus cavernosum SM cell possesses the ability to modulate the phenotype under hyperglycemic conditions, which could have a key role in the pathogenesis of diabetic erectile dysfunction.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Ponholzer A, Temml C, Mock K, Marszalek M, Obermayr R, Madersbacher S . Prevalence and risk factors for erectile dysfunction in 2869 men using a validated questionnaire. Eur Urol 2005; 47: 80–86.

    Article  Google Scholar 

  2. Cho NH, Ahn CW, Park JY, Ahn TY, Lee HW, Park TS et al. Prevalence of erectile dysfunction in Korean men with type 2 diabetes mellitus. Diabet Med 2006; 23: 198–203.

    Article  CAS  Google Scholar 

  3. Malavige LS, Levy JC . Erectile dysfunction in diabetes mellitus. J Sex Med 2009; 6: 1232–1247.

    Article  Google Scholar 

  4. Kapoor D, Clarke S, Channer KS, Jones TH . Erectile dysfunction is associated with low bioactive testosterone levels and visceral adiposity in men with type 2 diabetes. Int J Androl 2007; 30: 500–507.

    Article  CAS  Google Scholar 

  5. Roth A, Kalter-Leibovici O, Kerbis Y, Tenenbaum-Koren E, Chen J, Sobol T et al. Prevalence and risk factors for erectile dysfunction in men with diabetes, hypertension, or both diseases: a community survey among 1,412 Israeli men. Clin Cardiol 2003; 26: 25–30.

    Article  Google Scholar 

  6. Burchardt T, Burchardt M, Karden J, Buttyan R, Shabsigh A, de la Taille A et al. Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat. J Urol 2000; 164: 1807–1811.

    Article  CAS  Google Scholar 

  7. Ferrini MG, Kovanecz I, Sanchez S, Umeh C, Rajfer J, Gonzalez-Cadavid NF . Fibrosis and loss of smooth muscle in the corpora cavernosa precede corporal veno-occlusive dysfunction (cvod) induced by experimental cavernosal nerve damage in the rat. J Sex Med 2009; 6: 415–428.

    Article  CAS  Google Scholar 

  8. Owens GK, Kumar MS, Wamhoff BR . Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 2004; 84: 767–801.

    Article  CAS  Google Scholar 

  9. Orr AW, Lee MY, Lemmon JA, Yurdagul Jr A, Gomez MF, Bortz PD et al. Molecular mechanisms of collagen isotype-specific modulation of smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol 2009; 29: 225–231.

    Article  CAS  Google Scholar 

  10. Rzucidlo EM, Martin KA, Powell RJ . Regulation of vascular smooth muscle cell differentiation. J Vasc Surg 2007; 45 (Suppl A): A25–A32.

    Article  Google Scholar 

  11. Kovanecz I, Nolazco G, Ferrini MG, Toblli JE, Heydarkhan S, Vernet D et al. Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction. BJU Int 2009; 103: 1396–1404.

    Article  Google Scholar 

  12. Wei AY, Cheng Y, Li YG . Phenotype modulation of smooth muscle in corpus cavernosum in penis tunica albuginea in diabetes mellitus with erectile dysfunction: experiment with rats. Zhonghua Yi Xue Za Zhi 2007; 87: 3006–3011 (in Chinese).

    CAS  PubMed  Google Scholar 

  13. Yang R, Wang J, Chen Y, Sun Z, Wang R, Dai Y . Effect of caffeine on erectile function via up-regulating cavernous cyclic guanosine monophosphate in diabetic rats. J Androl 2008; 29: 586–591.

    Article  CAS  Google Scholar 

  14. Chen Y, Li SX, Yao LS, Wang R, Dai YT . Valsartan treatment reverses erectile dysfunction in diabetic rats. Int J Impot Res 2007; 19: 366–370.

    Article  CAS  Google Scholar 

  15. Heaton JP, Varrin SJ, Morales A . The characterization of a bio-assay of erectile function in a rat model. J Urol 1991; 145: 1099–1102.

    Article  CAS  Google Scholar 

  16. Pilatz A, Schultheiss D, Gabouev AI, Schlote N, Mertsching H, Jonas U et al. Isolation of primary endothelial and stromal cell cultures of the corpus cavernosum penis for basic research and tissue engineering. Eur Urol 2005; 47: 710–719.

    Article  Google Scholar 

  17. Kropp BP, Zhang Y, Tomasek JJ, Cowan R, Furness III PD, Vaughan MB et al. Characterization of cultured bladder smooth muscle cells: assessment of in vitro contractility. J Urol 1999; 162: 1779–1784.

    Article  CAS  Google Scholar 

  18. Rensen SS, Doevendans PA, van Eys GJ . Regulation and characteristics of vascular smooth muscle cell phenotypic diversity. Neth Heart J 2007; 15: 100–108.

    Article  CAS  Google Scholar 

  19. Cheng Y, Liu X, Yang J, Lin Y, Xu DZ, Lu Q et al. Microrna-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res 2009; 105: 158–166.

    Article  CAS  Google Scholar 

  20. Neuville P, Geinoz A, Benzonana G, Redard M, Gabbiani F, Ropraz P et al. Cellular retinol-binding protein-1 is expressed by distinct subsets of rat arterial smooth muscle cells in vitro and in vivo. Am J Pathol 1997; 150: 509–521.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Beamish JA, Fu AY, Choi AJ, Haq NA, Kottke-Marchant K, Marchant RE . The influence of rgd-bearing hydrogels on the re-expression of contractile vascular smooth muscle cell phenotype. Biomaterials 2009; 30: 4127–4135.

    Article  CAS  Google Scholar 

  22. Hungerford JE, Owens GK, Argraves WS, Little CD . Development of the aortic vessel wall as defined by vascular smooth muscle and extracellular matrix markers. Dev Biol 1996; 178: 375–392.

    Article  CAS  Google Scholar 

  23. Miano JM, Cserjesi P, Ligon KL, Periasamy M, Olson EN . Smooth muscle myosin heavy chain exclusively marks the smooth muscle lineage during mouse embryogenesis. Circ Res 1994; 75: 803–812.

    Article  CAS  Google Scholar 

  24. Zhang X, Kanika ND, Melman A, Disanto ME . Smooth muscle myosin expression, isoform composition and functional activities in rat corpus cavernosum altered by the streptozotocin-induced type 1 diabetes. Am J Physiol Endocrinol Metab 2012; 302: E32–E42.

    Article  CAS  Google Scholar 

  25. Saleem MA, Zavadil J, Bailly M, McGee K, Witherden IR, Pavenstadt H et al. The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells. Am J Physiol Renal Physiol 2008; 295: F959–F970.

    Article  CAS  Google Scholar 

  26. Parekh A, Long RA, Iannone EC, Chancellor MB, Sacks MS . Assessing the effects of transforming growth factor-beta1 on bladder smooth muscle cell phenotype. I. Modulation of in vitro contractility. J Urol 2009; 182: 1210–1215.

    Article  CAS  Google Scholar 

  27. Hao H, Gabbiani G, Bochaton-Piallat ML . Arterial smooth muscle cell heterogeneity: implications for atherosclerosis and restenosis development. Arterioscler Thromb Vasc Biol 2003; 23: 1510–1520.

    Article  CAS  Google Scholar 

  28. Long X, Bell RD, Gerthoffer WT, Zlokovic BV, Miano JM . Myocardin is sufficient for a smooth muscle-like contractile phenotype. Arterioscler Thromb Vasc Biol 2008; 28: 1505–1510.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by Southern Medical University, China, Grant No.: 2008B014.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A-Y Wei.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wei, AY., He, SH., Zhao, JF. et al. Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction. Int J Impot Res 24, 196–201 (2012). https://doi.org/10.1038/ijir.2012.16

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijir.2012.16

Keywords

This article is cited by

Search

Quick links