ORIGINAL RESEARCH—BASIC SCIENCE: Profibrotic Role of Myostatin in Peyronie's Disease
Article first published online: 15 APR 2008
© 2008 International Society for Sexual Medicine
The Journal of Sexual Medicine
Volume 5, Issue 7, pages 1607–1622, July 2008
How to Cite
Cantini, L. P., Ferrini, M. G., Vernet, D., Magee, T. R., Qian, A., Gelfand, R. A., Rajfer, J. and Gonzalez-Cadavid, N. F. (2008), ORIGINAL RESEARCH—BASIC SCIENCE: Profibrotic Role of Myostatin in Peyronie's Disease. Journal of Sexual Medicine, 5: 1607–1622. doi: 10.1111/j.1743-6109.2008.00847.x
- Issue published online: 4 JUL 2008
- Article first published online: 15 APR 2008
- Stem Cells;
Introduction. The primary histologic finding in many urologic disorders, including Peyronie's disease (PD), is fibrosis, mainly mediated by the transforming growth factor β1 (TGFβ1).
Aim. To determine whether another member of the TGFβ family, myostatin, (i) is expressed in the human PD plaque and normal tunica albuginea (TA), their cell cultures, and the TGFβ1-induced PD lesion in the rat model; (ii) is responsible for myofibroblast generation, collagen deposition, and plaque formation; and (iii) mediates the profibrotic effects of TGFβ1 in PD.
Methods. Human TA and PD tissue sections, and cell cultures from both tissues incubated with myostatin and TGFβ1 were subjected to immunocytochemistry for myostatin and α-smooth muscle actin (ASMA). The cells were assayed by western blot, Real time-Polymerase chain reaction (RT-PCR), and ribonuclease protection. Myostatin cDNA and shRNA were injected, with or without TGFβ1, in the rat penile TA, and plaque size was estimated by Masson.
Main Outcome Measures. Myostatin expression in the human TA, the PD plaque, and their cell cultures, and myostatin effects on the PD-like plaque in the rat.
Results. A threefold overexpression of myostatin was found in the PD plaque as compared with the TA. In PD cells, myostatin expression was mainly in the myofibroblasts, and in the TA cells, it increased upon passage paralleling myofibroblast differentiation and was up-regulated by TGFβ1. Myostatin or its cDNA construct increased the myofibroblast number and collagen in TA cells. Myostatin was detected in the TGFβ1-induced PD-like plaque of the rat partly in the myofibroblasts, and in the TA. Myostatin cDNA injected in the TA induced a plaque and intensified the TGFβ1 lesion, which was not reduced by myostatin shRNA.
Conclusions. Myostatin is overexpressed in the PD plaque, partly because of myofibroblast generation. Although myostatin induces a plaque in the rat TA, it does not appear to mediate the one triggered by TGFβ1, thus suggesting that both proteins act concurrently and that therapy should target their common downstream effectors. Cantini LP, Ferrini MG, Vernet D, Magee TR, Qian A, Gelfand RA, Rajfer J, and Gonzalez-Cadavid NF. Profibrotic role of myostatin in Peyronie's disease. J Sex Med 2008;5:1607–1622.