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BOR - Papers in Press, published online ahead of print December 15, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.035089
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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-{beta}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-{beta}1 (TGF{beta}1) has been suggested to have an important role in cavernous fibrosis, and resultant erectile dysfunction. For further elucidation of TGF{beta}1 signaling in association with cavernous fibrosis, we developed a rat model of cavernous fibrosis using TGF{beta}1-producing NIH 3T3 fibroblasts (NIH 3T3-TGF{beta}1). NIH 3T3-TGF{beta}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{beta}1 cells (Group 3), whereas no histological evidence of cavernous fibrosis was found in the control rats (Group 1) or the recombinant human TGF{beta}1 protein injected rats (Group 2). Immunohistochemical staining revealed a higher expression of TGF{beta}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{beta}1 mRNA continued to 10 days after injection of the cells. NIH 3T3-TGF{beta}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{beta}1 signaling and the development of new therapeutics targeting this pathway.

Key words: Male sexual function • Penis





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