title: Prevention of esophageal stricture after endoscopic submucosal dissection using RNA-based silencing of carbohydrate sulfotransferase 15 in a porcine model.
abstract: Background and study aimsEndoscopic 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 methodsTwo 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.ResultsOn 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.ConclusionCHST15 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.
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Sagara
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Nakajima
authors.affiliation: Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Stelic Institute & Co. Inc., Minato City, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoneyama
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.affiliation: Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Yahagi
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000069916:Endoscopic Mucosal Resection / Q000009:adverse effects; D000071041:Esophageal Mucosa / Q000473:pathology* / Q000601:surgery; D004940:Esophageal Stenosis / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004945:Esophagoscopy; D005260:Female; D005355:Fibrosis; D020868:Gene Silencing; D015552:Injections, Intralesional; D058628:Myofibroblasts; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000627:therapeutic use*; D015238:Sulfotransferases / Q000235:genetics*; D013552:Swine; D016212:Transforming Growth Factor beta / Q000235:genetics; D014456:Ulcer / Q000188:drug therapy / Q000209:etiology
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D015238:Sulfotransferases