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.

Myostatin, a profibrotic factor and the main inhibitor of striated muscle mass, is present in the penile and vascular smooth muscle

Abstract

Myostatin is present in striated myofibers but, except for myometrial cells, has not been reported within smooth muscle cells (SMC). We investigated in the rat whether myostatin is present in SMC within the penis and the vascular wall and, if so, whether it is transcriptionally expressed and associated with the loss of corporal SMC occurring in certain forms of erectile dysfunction (ED). Myostatin protein was detected by immunohistochemistry/fluorescence and western blots in the perineal striated muscles, and also in the SMC of the penile corpora, arteries and veins, and aorta. Myostatin was found in corporal SMC cultures, and its transcriptional expression (and its receptor) was shown there by DNA microarrays. Myostatin protein was measured by western blots in the penile shaft of rats subjected to bilateral cavernosal nerve resection (BCNR), that were left untreated, or treated (45 days) with muscle-derived stem cells (MDSC), or concurrent daily low-dose sildenafil. Myostatin was not increased by BCNR (compared with sham operated animals), but over expressed after treatment with MDSC. This was reduced by concurrent sildenafil. The presence of myostatin in corporal and vascular SMC, and its overexpression in the corpora by MDSC therapy, may have relevance for the stem cell treatment of corporal fibrosis and ED.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

References

  1. 1

    Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci USA 1998; 95: 14938–14943.

    CAS  Article  Google Scholar 

  2. 2

    Dschietzig TB . Myostatin - From the Mighty Mouse to cardiovascular disease and cachexia. Clin Chim Acta 2014; 433: 216–224.

    CAS  Article  Google Scholar 

  3. 3

    McPherron AC, Lawler AM, Lee SJ . Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997; 387: 83–90.

    CAS  Article  Google Scholar 

  4. 4

    Reisz-Porszasz S, Bhasin S, Artaza JN, Shen R, Sinha-Hikim I, Hogue A et al. Lower skeletal muscle mass in male transgenic mice with muscle-specific over expression of myostatin. Am J Physiol Endocrinol Metab 2003; 285: E876–E888.

    CAS  Article  Google Scholar 

  5. 5

    Magee TR, Artaza JN, Ferrini MG, Vernet D, Zuniga FI, Cantini L et al. Myostatin short interfering hairpin RNA gene transfer increases skeletal muscle mass. J Gene Med 2006; 8: 1171–1181.

    CAS  Article  Google Scholar 

  6. 6

    Lieber RL, Ward SR . Cellular mechanisms of tissue fibrosis. 4. Structural and functional consequences of skeletal muscle fibrosis. Am J Physiol Cell Physiol 2013; 305: C241–C252.

    CAS  Article  Google Scholar 

  7. 7

    Kharraz Y, Guerra J, Pessina P, Serrano AL, Muñoz-Cánoves P . Understanding the process of fibrosis in Duchenne muscular dystrophy. Biomed Res Int 2014; 2014: 965631.

    Article  Google Scholar 

  8. 8

    Artaza JN, Reisz-Porszasz S, Dow JS, Kloner RA, Tsao J, Bhasin S et al. Alterations in myostatin expression are associated with changes in cardiac left ventricular mass but not ejection fraction in the mouse. J Endocrinol 2007; 194: 63–76.

    CAS  Article  Google Scholar 

  9. 9

    Argilés JM, Orpí M, Busquets S, López-Soriano FJ . Myostatin: more than just a regulator of muscle mass. Drug Discov Today 2012; 17: 702–709.

    Article  Google Scholar 

  10. 10

    Shenoy PS, Bose B, Sharma M, McFarlane C, Kambadur R . Lack of myostatin reduces MyoD induced myogenic potential of primary muscle fibroblasts. J Cell Biochem 2014; 115: 1908–1917.

    Google Scholar 

  11. 11

    Guo T, Jou W, Chanturiya T, Portas J, Gavrilova O, McPherron AC . Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PLoS One 2009; 4: e4937.

    Article  Google Scholar 

  12. 12

    Ciarmela P, Islam MS, Reis FM, Gray PC, Bloise E, Petraglia F et al. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Hum Reprod Update 2011; 17: 772–790.

    CAS  Article  Google Scholar 

  13. 13

    Ciarmela P, Wiater E, Smith SM, Vale W . Presence, actions, and regulation of myostatin in rat uterus and myometrial cells. Endocrinology 2009; 150: 906–914.

    CAS  Article  Google Scholar 

  14. 14

    Cantini LP, Ferrini MG, Vernet D, Magee TR, Quian A, Gelfand RA et al. Profibrotic role of myostatin in Peyronie's disease. J Sex Med 2008; 5: 1607–1622.

    CAS  Article  Google Scholar 

  15. 15

    Gelfand RA, Vernet D, Kovanecz I, Rajfer J, Gonzalez-Cadavid NF . The transcriptional signatures of cells from the human peyronie's disease plaque and the ability of these cells to generate a plaque in a rat model suggest potential therapeutic targets. J Sex Med 2015; 12: 313–327.

    CAS  Article  Google Scholar 

  16. 16

    Tsao J, Kovanecz I, Awadalla N, Gelfand R, Sinha Hickim I, White RA et al. Muscle derived stem cells stimulate muscle myofiber repair and counteract fat infiltration in a diabetic mouse model of critical limb ischemia. J Stem Cell Res Ther 2016; 6, pii 370.

    PubMed  PubMed Central  Google Scholar 

  17. 17

    Kovanecz I, Rivera S, Nolazco G, Vernet D, Segura D, Gharib S et al. Separate or combined treatments with daily sildenafil, molsidomine, or muscle-derived stem cells prevent erectile dysfunction in a rat model of cavernosal nerve damage. J Sex Med 2012; 9: 2814–2826.

    CAS  Article  Google Scholar 

  18. 18

    Vernet D, Kovanecz I, Masouminia M, Loni L, Aboagye J, Rajfer J et al. Induced pluripotent stem cells (iPS) ameliorate corporal veno-occlusive dysfunction (CVOD) in a rat model of bilateral cavernosal nerve resection (BCNR). J Sex Med 2015; 12-S2: 178.

    Google Scholar 

  19. 19

    Artaza JN, Bhasin S, Magee TR, Reisz-Porszasz S, Shen R, Groome NP et al. Myostatin inhibits myogenesis and promotes adipogenesis in C3H 10T(1/2) mesenchymal multipotent cells. Endocrinology 2005; 146: 3547–3557.

    CAS  Article  Google Scholar 

  20. 20

    Kovanecz I, Gelfand R, Masouminia M, Gharib S, Segura D, Vernet D et al. Oral Bisphenol A (BPA) given to rats at moderate doses is associated with erectile dysfunction, cavernosal lipofibrosis and alterations of global gene transcription. Int J Impot Res 2014; 26: 67–75.

    CAS  Article  Google Scholar 

  21. 21

    Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez-Cadavid NF . Serum myostatin-immuno-reactive protein is increased in 60-92 year old women and men with muscle wasting. J Nutr Health Aging 2002; 6: 343–348.

    CAS  PubMed  Google Scholar 

  22. 22

    Singh R, Braga M, Pervin S . Regulation of brown adipocyte metabolism by myostatin/ follistatin signaling. Front Cell Dev Biol 2014; 2: 60.

    PubMed  PubMed Central  Google Scholar 

  23. 23

    Zhang C, Tan CK, McFarlane C, Sharma M, Tan NS, Kambadur R . Myostatin-null mice exhibit delayed skin wound healing through the blockade of transforming growth factor-β signaling by decorin. Am J Physiol Cell Physiol 2012; 302: C1213–C1225.

    CAS  Article  Google Scholar 

  24. 24

    Gonzalez-Cadavid NF, Bhasin S . Role of myostatin in metabolism. Curr Opin Clin Nutr Metab Care 2004; 7: 451–457.

    CAS  Article  Google Scholar 

  25. 25

    Artaza JN, Singh R, Ferrini MG, Braga M, Tsao J, Gonzalez-Cadavid NF . Myostatin promotes a fibrotic phenotypic switch in multipotent C3H 10T1/2 cells without affecting their differentiation into myofibroblasts. J Endocrinol 2008; 196: 235–249.

    CAS  Article  Google Scholar 

  26. 26

    Mendler L, Baka Z, Kovács-Simon A, Dux L . Androgens negatively regulate myostatin expression in an androgen-dependent skeletal muscle. Biochem Biophys Res Commun 2007; 361: 237–242.

    CAS  Article  Google Scholar 

  27. 27

    Verhovshek T, Cai Y, Osborne MC, Sengelaub DR . Androgen regulates brain- derived neurotrophic factor in spinal motoneurons and their target musculature. Endocrinology 2010; 151: 253–261.

    CAS  Article  Google Scholar 

  28. 28

    Dubois V, Laurent MR, Sinnesael M, Cielen N, Helsen C, Clinckemalie L et al. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle. FASEB J 2014; 28: 2979–2994.

    CAS  Article  Google Scholar 

  29. 29

    Ranson RN, Connelly JH, Santer RM, Watson AH . Nuclear expression of PG-21, SRC-1, and pCREB in regions of the lumbosacral spinal cord involved in pelvic innervation in young adult and aged rats. Anat Cell Biol 2012; 45: 241–258.

    Article  Google Scholar 

  30. 30

    Gao C, Xiong W, Li Y . The myofibrosis mechanism of differentiation growth factor-8 on rat abdominal aorta grafts. Transplant Proc 2007; 39: 3420–3423.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a grant from the American Diabetes Association (#7- 12-BS-062) and by a grant of the Norris Foundation, both to NGC.

Author information

Affiliations

Authors

Corresponding author

Correspondence to N F Gonzalez-Cadavid.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kovanecz, I., Masouminia, M., Gelfand, R. et al. Myostatin, a profibrotic factor and the main inhibitor of striated muscle mass, is present in the penile and vascular smooth muscle. Int J Impot Res 29, 194–201 (2017). https://doi.org/10.1038/ijir.2017.22

Download citation

Further reading

Search

Quick links