IN-1233, an ALK-5 inhibitor: Prevention of granulation tissue formation after bare metallic stent placement in a rat urethral model

Purpose: To evaluate the efficacy of an activin receptor-like kinase-5 inhibitor, IN-1233, for the prevention of tissue hyperplasia after bare stent placement in a rat urethral model. Materials and Methods: Procedures were performed in accordance with the National Institutes of Health guidelines for humane handling of animals; approval of the committee of animal research was obtained. In 20 Sprague-Dawley male rats (weight range, 300-350 g), a self-expanding metallic bare stent was inserted in the urethra by using fluoroscopic guidance. One group of 10 rats (group A) was treated with IN-1233, the other group of 10 rats (group B) received no treatment. Retrograde urethrography was performed 4 and 8 weeks after stent placement. All rats were sacri-ficed at 8 weeks for histologic analysis. Results: Stent placement was technically successful in all rats. The average stent diameter was significantly larger in group A compared with group B at follow-up retrograde urethrography performed 4(P =.006) and 8(P < .001) weeks after stent placement. At histologic analysis, the percentage of granulation tissue area(P < .001), thickness of submucosal fibrosis ( P < .001), and number of epithelial layers(P < .001) were significantly decreased in group A compared with group B. Inflammatory cell infiltration(P < .001) was significantly increased in group A compared with group B. Conclusion: IN-1233 is effective for the prevention of granulation tissue formation after bare metallic stent placement in a rat urethral model.