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-¥â1
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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-¥â1 (TGF-¥â1) 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-¥â signaling pathway in cavernous fibrosis, we established a rat model of cavernous fibrosis by using adenovirus expressing TGF-¥â1 (ad-TGF-¥â1). Materials and
Methods: Four-month-old male Sprague-Dawley rats received intracavernous injection of ad-TGF-¥â1 (1¡¿108, 1¡¿109, or 1¡¿1010 virus particles [vp] in 100 ¥âl 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 ¥âl); and Group 3, intracavernous injection of ad-TGF-¥â1 (1¡¿1010 vp/100 ¥âl). 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 ¥â-actin.
Results: Masson¡¯s trichrome staining revealed that intracavernous delivery of ad-TGF-¥â1 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 ¥âl), whereas no histologic evidence of cavernous fibrosis was found in the control rats or the ad-LacZ-injected rats. The rats receiving ad-TGF-¥â1 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-¥â1 compared with that in controls or rats receiving ad-LacZ.
Conclusions: This model induced by ad-TGF-¥â1 may play an important role in understanding the pathophysiologic mechanisms of cavernous fibrosis-associated TGF-¥â signaling and the development of new therapeutics targeting this pathway.
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KEYWORD
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Erectile dysfunction, Transforming growth factor-¥â, Penis, Fibrosis
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