## 3 Results
### Effect of the Drug on Protein Expression  
Figure 3 shows the Western blotting results. EW-7197 treatment for 3 weeks significantly suppressed the expression of the profibrogenic proteins TGF-\(\beta\)1, pSmad3, and \(\alpha\)-SMA. We found that the expression of these proteins increased significantly in the control group compared with the treatment group (\(p\) < 0.05). Figure 1: Fluoroscopic esophagogram with contrast media at 3 weeks after surgery. The stenosis ratio was determined by comparing the axial diameter in both the upper undamaged area and the lower stenosis area. Healthy rat; rat with corrosive burn but without TGF-\(\beta\)1 inhibitor treatment (control); rat with corrosive burn and with TGF-\(\beta\)1 inhibitor treatment (treatment) ((**A**–**C**), respectively). The figure demonstrates significantly less esophageal stenosis in the treatment group compared with the control group (\(p\) = 0.001). Figure 2: [PERSON]’s trichrome stain was used for fibrosis determination. Healthy rat; rat with corrosive burn but without TGF-\(\beta\)1 inhibitor treatment (control); rat with corrosive burn and with TGF-\(\beta\)1 inhibitor treatment (treatment) ((**A**–**C**), respectively). The fibrosis area ratio was significantly lower in the treatment group than that in the control group (\(p\) = 0.001). Our study demonstrated that the stenosis ratio determined by the fluoroscopic study and the fibrosis area ratio determined by histology analysis were significantly lower in the treatment group than those in the control group. Although we did not perform quantitative analysis, the expression patterns of profibrogenic proteins such as pSmad3 and \(\alpha\)-SMA were suppressed in the treatment group in our Western blot analysis. This result indicates that EW-7197 suppressed stricture formation by inhibiting TGF-\(\beta\)1/Smad3-induced ECM synthesis. Our results are consistent with previous studies performed in various animal models [14; 15; 16; 18]. However, our results were not directly connected to the improvement of survival or symptoms. Survival rates at 3 weeks after surgery were the same (70%) in both groups. In addition, the occurrence rate of esophageal stricture-related symptoms was 42.9% in the control group and 57.1% in the treatment group. Moreover, three rats in the treatment group died in the first week after surgery due to esophageal perforation. TGF-\(\beta\) could be responsible, not only for wound scarring but also for wound healing. The key roles of TGF-\(\beta\) in wound healing including production and remodeling of the ECM, which is crucial for tissue damage repair. We surmise that the treatment group experienced delayed wound healing and fibrosis inhibition in the injured segment, which led to esophageal perforation. It is already well known that fibroblast proliferation and collagen deposition occur in the second week after injury, representing the biological pathway of stricture formation [25]. More research is needed to investigate complex etiological causes in acute and subacute periods of corrosive burns. Our study included some limitations. First, we excluded three rats that died due to their debilitating status because they did not survive until their scheduled sacrifice date. However, because these rats may have represented the most severe corrosive injury cases, this could have biased the results. Nevertheless, we believe these deaths were consequences of severe injury, rather than death related to stricture formation, because the timing of the deaths was concentrated in the first week after the corrosive burn. Second, it is possible that peritoneal adhesion formation after surgery may have affected the fluoroscopic results. We used a modified version of [PERSON] and [PERSON]'s experimental model, the most commonly used model in previous studies [26]. In this model, the lower esophagus is dissected and ligated to prevent leakage of the caustic substance. Adhesion between the serosa of the esophagus and peritoneum occurred during the healing period.