Korean J Androl.  2009 Aug;27(2):82-88.

Effect of IN-1130, a Novel Transforming Growth Factor-beta Type I Receptor Kinase (ALK5) Inhibitor, on a Rat Model of Peyronie's Disease Induced by Repeated Intratunical Injections of Fibrin

• Piao S
• Tumurbaatar M
• Oh JH
• Park SH
• Suh JK
• Ryu JK

Abstract

PURPOSE: Transforming growth factor-beta1 (TGF-beta1) has been known to be involved in the pathogenesis of Peyronie's disease (PD). In the present study, we investigated the therapeutic effect of IN-1130, a novel small molecule inhibitor of activin receptor-like kinase (ALK)5, a type I receptor of TGF-beta, in an animal model of PD induced by fibrin.
MATERIALS AND METHODS
Four-month-old male Sprague-Dawley rats were divided into three groups (n=4 per group): group 1, age-matched control; group 2, PD rats without treatment; group 3, PD rats receiving an intratunical injection of IN-1130 (on day 20, 5 mg/kg in 0.1 ml saline) into the lesion. PD was induced in rats through repeated injections of fibrin (50 microliter each of human fibrin and thrombin solutions, days 0, 3, and 6, respectively) into the tunica albuginea. Penile curvature was evaluated by use of an artificialerection test on day 30. The penis was then harvested and stained with Masson trichrome, hematoxylin- eosin, and antibody to vimentin and phospho-Smad2.
RESULTS
PD rats receiving repeated intratunical injections of fibrin revealed an infiltration of inflammatory cells, including lymphocytes, plasma cells, and fibroblasts, and an increase in transnuclear expression of phospho-Smad2 in the fibrotic plaque. However, repeated intratunical injections of fibrin did not induce penile curvature. IN-1130 induced significant regression of fibrotic plaque through reduced infiltration of inflammatory cells and reduced transnuclear expression of phospho-Smad2.
CONCLUSIONS
Inhibition of TGF-beta pathway through the use of ALK5 inhibitors may be a curative local treatment modality for PD.

Keyword

Penile induration; Fibrin; Transforming growth factor-beta; ALK5; IN-1130

MeSH Terms

Activin Receptors
Animals
Eosine Yellowish-(YS)
Fibrin
Fibroblasts
Humans
Imidazoles
Lymphocytes
Male
Models, Animal
Penile Induration
Penis
Phosphotransferases
Plasma Cells
Quinoxalines
Rats
Rats, Sprague-Dawley
Thrombin
Transforming Growth Factor beta
Vimentin
Activin Receptors
Eosine Yellowish-(YS)
Fibrin
Imidazoles
Phosphotransferases
Quinoxalines
Thrombin
Transforming Growth Factor beta
Vimentin