TGF-ß1 inhibitor P144 protects against benign restenosis after esophageal stenting through TGF-ß1/Smads signaling pathway inhibition.

ABSTRACT

BACKGROUND AND STUDY AIMS: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-ß1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-ß1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-ß1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-ß1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent. MATERIAL AND METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-ß1 with or without TGF-ß1 inhibitor P144. RESULTS: The serum level of IL-1ß and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-ß1, and obviously decreased when treated with P144. CONCLUSIONS: TGF-ß1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-ß1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.