Effects of Antisense TGF-beta1 Oligodeoxynucleotides on Formation of Stricture in Injured Urethral of Rats

Rim, Joung Sik; Seo, Il Young; Kim, Jong Sung; Chung, Hun Taeg

Abstract

Transforming growth factor-B1(TGF-B1) has many fundamental biological processes including cell growth, extracellular matrix deposition and degradation, and inflammatory responses. TGF-B1 is released by platelet and inflammatory cells, and it affects all phases of wound healing after injury. It contributes to the regulation of fibroblast chemotaxis and proliferation, and also controls the synthesis and degradation of extracellular matrix necessary for tissue repair. Clinically, scar tissue formation and subsequent stricture after urethral injury frequently results in troublesome problems to urologists. In the phase I study of this report, we intended to how the histological changes and the involvement of TGF-B1 in the formation of stricture in injured urethrae of rats. We injured urethrae of 24 adult male Sprauge-Dawley rats(200-250 g.) by urethrotome and Dormia basket and then observed histological changes and analysed TGF-f, mRNA levels of the injured urethrae by Northern blot. Northern b1ot analysis showed that TGF-t, mRNA was much expressed on day 1,3,5 after injury. Fibroblasts and deposition of extracellular matrix were markedly increased on day 5. Reepithelialization was completed and urethral lumen was narrowed on day 10. In the phase II study, we tried to know that antisense TGF-B1 oligodeoxynucleotides(ODNs) could inhibit TGF-B1 expression and the formation of stricture in injured urethrae of rats. We injured urethrae of rats and treated the urethral injury with the application of antisense TGF-B1 ODNs. Northern blot analysis showed that TGF-B1 mRNA was little expressed in the urethrae treated with the antisense on day 1,3 after injury. Comparing to the antisense-nontreated urethrae, the antisense-treated urethrae showed decrease of submucosal thickening and maintained normal sized urethral lumens on day 14, 21 after injury. In conclusion, increase of TGF-B1 mRNA in injured urethrae of rats suggests that TGF-B1 could play an important role in repair mechanism. With application of antisense TGF-B1 ODNs in injured urethrae of rats, the expression of TGF-B1 can be inhibited and also the formation of stricture prevented.