Prevention of esophageal stricture after endoscopic submucosal dissection using RNA-based silencing of carbohydrate sulfotransferase 15 in a porcine model.

Abstract

Background and study aims Endoscopic submucosal dissection (ESD) for esophageal carcinoma frequently causes fibrotic strictures that require treatment. A possible preventive effect of small interfering RNA (siRNA) targeting carbohydrate sulfotransferase 15 (CHST15) on esophageal stricture formation after ESD was investigated in 3 pigs. Materials and methods Two half-circumferential ESD ulcers were created in the oral and anal ends of the esophagus. CHST15 siRNA was injected submucosally in one of the two ESD ulcers. Endoscopic, macroscopic, histological, and polymerase chain reaction analyses were performed. Results On post-operative day 14, the non-treated ulcers were found to show histological fibrosis and increased expression of the CHST15 messenger RNA. A single endoscopic injection of CHST15 siRNA alleviated stricture development in post-ESD ulcers with significant reduction in the mucosal contraction rate. The deposition of collagen and accumulation of fibroblasts and myofibroblasts were diminished in ulcers treated with CHST15 siRNA, where significant suppression of CHST15, transforming growth factor-beta (TGF-β), and collagen-1 messenger RNAs was also seen. Conclusion CHST15 siRNA alleviated esophageal post-ESD stricture formation via repression of fibrosis, revealing a novel therapeutic role for antifibrotic agents in the prevention of post-ESD strictures.