Submitted August 10, 2004
Returned for revision September 20, 2004
Accepted November 16, 2004
Male Reproductive Tract
Establishment of Penile Fibrosis Model in a Rat Using
Mouse NIH 3T3 Fibroblasts Expressing Transforming Growth
Factor-
1
Ji-Kan Ryu ,
Sun U. Song ,
Jee-Young Han ,
Young-Chae Chu ,
Minhyung Lee ,
Jun-Sig Kim ,
Seong-Jin Kim ,
and
Jun-Kyu Suh *
* To whom correspondence should be addressed. E-mail: jksuh{at}inha.ac.kr.
Abstract
Transforming growth factor-
1 (TGF
1) has been
suggested to have an important role in cavernous fibrosis,
and resultant erectile dysfunction. For further
elucidation of TGF
1 signaling in association with
cavernous fibrosis, we developed a rat model of cavernous
fibrosis using TGF
1-producing NIH 3T3 fibroblasts
(NIH 3T3-TGF
1). NIH 3T3-TGF
1 cells were
injected into male Sprague-Dawley rats intracavernously.
Masson's trichrome staining at 20 days postinjection
showed multiple fibrous scars in the rats injected with
the NIH 3T3-TGF
1 cells (Group 3), whereas no
histological evidence of cavernous fibrosis was found in
the control rats (Group 1) or the recombinant human
TGF
1 protein injected rats (Group 2).
Immunohistochemical staining revealed a higher expression
of TGF
1 and its type II receptor in group 3 than in
groups 1 or 2. Electrostimulation of the cavernous nerve
revealed that the maximal intracavernous pressure was
significantly lower in group 3 than in groups 1 or 2
(P<0.01). The expression of transgenic TGF
1
mRNA continued to 10 days after injection of the cells.
NIH 3T3-TGF
1 cells sufficiently induced relatively
long-lasting cavernous fibrosis. This novel animal model
may contribute to the future investigations of the
pathogenesis of penile fibrosis associated with
TGF
1 signaling and the development of new
therapeutics targeting this pathway.
Key words:
Male sexual function
Penis