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KMID : 0356420100280020100
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Journal of Korean Andrology
2010 Volume.28 No. 2 p.100 ~ p.106
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Establishment of a Cavernous Fibrosis Model in a Rat Using Adenovirus Expressing Transforming Growth Factor-β1
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Ryu Ji-Kan
Oh Seing-Min
Hai Rong-Jin
Kim Do-Kyung
Kang Yong-Jin
Jang Jin-Hyuk
Suh Jun-Kyu
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Abstract
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Purpose: Transforming growth factor-β1 (TGF-β1) has been implicated in cavernous fibrosis due to a variety of causes of erectile dysfunction (ED), such as diabetes mellitus and post-radical prostatectomy. To examine the role of the TGF-β signaling pathway in cavernous fibrosis, we established a rat model of cavernous fibrosis by using adenovirus expressing TGF-β1 (ad-TGF-β1). Materials and
Methods: Four-month-old male Sprague-Dawley rats received intracavernous injection of ad-TGF-β1 (1×108, 1×109, or 1×1010 virus particles [vp] in 100 βl of PBS) and the penis was harvested for histologic examination at 10, 20, or 30 days after injection (n=4 per group and per time point). Based on the initial findings, the animals were divided into three groups (n=6 per group): Group 1, age-matched control; Group 2, intracavernous injection of ad-LacZ (1×1010 vp/100 βl); and Group 3, intracavernous injection of ad-TGF-β1 (1×1010 vp/100 βl). At 30 days after injection, erectile function was evaluated during electrical stimulation of the cavernous nerve. The penis was then harvested and stained with Masson’s trichrome and antibody to smooth muscle β-actin.
Results: Masson’s trichrome staining revealed that intracavernous delivery of ad-TGF-β1 sufficiently induced cavernous fibrosis in a dose-dependent manner. The fibrotic scars persisted up to 30 days after injection at the highest dosage (1×1010 vp/100 βl), whereas no histologic evidence of cavernous fibrosis was found in the control rats or the ad-LacZ-injected rats. The rats receiving ad-TGF-β1 showed a higher cavernous collagen content and less smooth muscle content than the control rats or ad-LacZ-injected rats. Erectile function was significantly decreased in rats receiving ad-TGF-β1 compared with that in controls or rats receiving ad-LacZ.
Conclusions: This model induced by ad-TGF-β1 may play an important role in understanding the pathophysiologic mechanisms of cavernous fibrosis-associated TGF-β signaling and the development of new therapeutics targeting this pathway.
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KEYWORD
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Erectile dysfunction, Transforming growth factor-β, Penis, Fibrosis
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