Fibrin as an inducer of fibrosis in the tunica albuginea of the rat: a new animal model of Peyronie's disease
Article first published online: 23 MAY 2003
Volume 91, Issue 9, pages 830–838, June 2003
How to Cite
Davila, H.H., Ferrini, M.G., Rajfer, J. and Gonzalez-Cadavid, N.F. (2003), Fibrin as an inducer of fibrosis in the tunica albuginea of the rat: a new animal model of Peyronie's disease. BJU International, 91: 830–838. doi: 10.1046/j.1464-410X.2003.04224.x
- Issue published online: 23 MAY 2003
- Article first published online: 23 MAY 2003
- Accepted for publication 25 January 2003
- penile trauma;
- plasmin activator inhibitor;
- reactive oxygen species
To investigate the role of fibrin in inducing fibrosis in the tunica albuginea (TA) of the rat penis, to develop a new animal model for Peyronie's disease (PD).
MATERIALS AND METHODS
The TA of rats (five per group per period) were injected with either saline, fibrin, transforming growth factor-β1 (TGF-β1) or TGF-β1 plus fibrin; the rats were killed at 1, 3, and 6 weeks after injection. Images were analysed quantitatively from tissue sections stained for collagen (Masson trichrome), fibrin (Verhoeff's stain) and elastin (Hart's stain), and immunostained for TGF-β1, inducible nitric oxide synthase (iNOS), heme oxygenase 1 (HO1), α-smooth muscle actin (ASMA), apoptosis (TUNEL) and plasminogen activator inhibitor (PAI). Collagen fibre organization was characterized by electron microscopy. Human PD plaque tissue and normal human TA were assayed for fibrin by immunohistochemistry in nine samples.
At 1 week after injection of fibrin into the rat TA, only oedema was present; at 3 weeks, the oedema developed into a characteristic fibrotic PD-like plaque. The injection of TGF-β1 into the TA also induced oedema in the TA at 1 and 3 weeks but there was very little evidence of a recognisable plaque at either time. Injection with TGF-β1 plus fibrin resulted in oedema at 1 week but at 3 weeks there was a smaller plaque than with fibrin only. At 6 weeks the induced plaques in the fibrin-only and fibrin + TGF-β1 groups persisted, and were comparable with those elicited at this time by TGF-β1 alone. The control animals showed no pathology at any of the sample times. At 3 weeks the PD plaque induced by injection with fibrin alone had not only greater expression of TGF-β1 than the TA of the animals receiving TGF-β1 alone, but also greater levels of other markers of fibrosis, e.g. HO1 (reactive oxygen species), ASMA (presence of myofibroblasts), apoptosis, and PAI (inhibitor of fibrinolysis). iNOS, a known antifibrotic agent, was also increased. In human PD plaque tissue, fibrin was detected by immunohistochemistry in all nine specimens.
These results suggest that fibrin, when introduced into the TA of the rat penis, acts as a potential profibrotic protein, possibly via the local release of TGF-β1, and induces a plaque not only histologically similar to that induced by TGF-β1 but to that of the human condition. Because fibrin can extravasate from the blood into the human TA after an injury to the TA, and because fibrin persists in the plaque tissue, we hypothesise that fibrin may play a key role in the pathogenesis of human PD.