Repeated intratunical injection of adenovirus expressing transforming growth factor-beta1 in a rat induces penile curvature with tunical fibrotic plaque: a useful model for the study of Peyronie's disease.
This study was undertaken to establish a Peyronie's disease model with penile curvature by using recombinant transforming growth factor-beta1 (TGF-beta1) protein or adenovirus (ad-TGF-beta1). Four-month-old male Sprague-Dawley rats were divided into seven groups (n = 18 per group): G1 received a single injection of saline into the tunica albuginea (0.1 mL); G2, repeated injections of ad-LacZ (days 0, 3, and 6; 1 x 10(10) particles/0.1 mL respectively); G3, a single injection of recombinant TGF-beta1 protein (700 ng/0.1 mL); G4, repeated injections of recombinant TGF-beta1 protein (days 0, 3 and 6; 700 ng/0.1 mL respectively); G5, a single injection of low-dose ad-TGF-beta1 (1 x 10(10) particles/0.1 mL); G 6, a single injection of high-dose ad-TGF-beta1 (3 x 10(10) particles/0.1 mL); and G7, repeated injections of low-dose ad-TGF-beta1 (days 0, 3, and 6; 1 x 10(10) particles/0.1 mL respectively). Penile curvature was evaluated 30, 45 and 60 days after treatment, and the penis was then harvested for histological examination. Repeated injection of low-dose ad-TGF-beta1 not only induced fibrous scar in the tunica, which lasted up to 60 days after injection, but also resulted in significant penile curvature by artificial erection test 45 days after treatment. A peculiar histological finding in this group was trapping of inflammatory cells in the tunica, subsequent fibrosis, and formation of cartilage and calcification as well as loss of elastin fibres. This model involving repeated injection of ad-TGF-beta1 may contribute to further investigation of the pathogenesis of Peyronie's disease and the development of new therapeutics targeting this pathway.
Piao
Shuguang
S
Department of Urology, Inha University School of Medicine, Incheon, Korea.
Ryu
Ji-Kan
JK
Shin
Hwa-Yean
HY
Zhang
Luwei
L
Song
Sun U
SU
Han
Jee-Young
JY
Park
Seok Hee
SH
Kim
Joon Mee
JM
Kim
In-Hoo
IH
Kim
Seong-Jin
SJ
Suh
Jun-Kyu
JK
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002114:Calcinosis / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004549:Elastin / Q000378:metabolism; D005355:Fibrosis; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007267:Injections; D008297:Male; D010410:Penile Erection; D010411:Penile Induration / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D010413:Penis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013552:Swine; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*
D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D004549:Elastin