Experimental models of Peyronie's disease. Implications for new therapies.
BACKGROUND
Despite its high prevalence and impact on the quality of life of patients, and that it is an excellent model for the study of fibrotic processes, Peyronie's disease (PD) is an orphan disease in biomedical research. The development of animal and cell culture models has advanced substantially the understanding of its molecular and cellular pathology and the proposal of new therapies.


OBJECTIVE
To review the literature pertaining to the use of these models for the study of PD.


METHODS
PubMed search conducted from the first report of an animal model for PD.


RESULTS
This model, based on the finding that transforming growth factor beta1 (TGF beta 1) is overexpressed in the PD plaque, consists on the injection of TGF beta 1 into the tunica albuginea of the rat. This leads to a PD-like plaque retaining many of the histological and biochemical features of human PD. Another rat model, based on the hypothesis that the PD plaque arises from trauma to the penis, causing fibrinogen extravasation that initiates as fibrin a fibrotic response, consists on injection of fibrin into the tunica. The cell culture model is based on the demonstration that myofibroblasts are abundant in the human PD plaque.


CONCLUSIONS
These models have: (i) clarified the role of microtrauma, myofibroblasts, and oxidative stress in plaque development; (ii) demonstrated that this tissue is under sustained turnover by fibrotic and antifibrotic mechanisms; (iii) showed the interplay of collagenolytic and fibrinolytic systems and their inhibitors; (iv) detected an endogenous antifibrotic process consisting of the expression of inducible nitric oxide synthase that counteracts oxidative stress, collagen synthesis, and myofibroblast generation; (v) characterized the antifibrotic effects of chronic treatment with phosphodiesterase type 5 (PDE5) inhibitors; (vi) discovered the cytogenetic instability of PD cells and alterations in their gene expression; and (vii) detected stem cells in the tunica albuginea with a potential role in fibrosis and ossification.
Gonzalez-Cadavid
Nestor F
NF
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center-Urology Research Laboratory, Torrance, CA, USA. ncadavid@ucla.edu
Rajfer
Jacob
J
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003078:Colchicine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005355:Fibrosis / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010411:Penile Induration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D051381:Rats; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology / Q000627:therapeutic use
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010726:Phosphodiesterase Inhibitors; D016212:Transforming Growth Factor beta; D050257:Tubulin Modulators; C022994:cyclic GMP-binding protein; D019001:Nitric Oxide Synthase; D003078:Colchicine