Since the first report of esophageal stent implantation in the 1970s, esophageal stenting has been an effective and minimally invasive treatment for benign and malignant esophageal strictures [1], [2]. However, benign restenosis after stent implantation is one of the important reasons for the clinical prognosis of such patients. Previous studies have reported that the incidence of benign restenosis after esophageal stent graft implantation reached 35 %, and the rate of restenosis after bare stent could be as high as 60 %, which seriously affects the clinical efficacy of stent implantation and the patient's quality of life [3], [4], [5]. It is difficult to removal of the stent when esophageal tissue hyperplasia causes esophageal stricture, which could cause severe esophageal hemorrhage or perforation of the esophagus [6], [7]. Therefore, it is of great clinical significance to study the pathological mechanism of benign restenosis after esophageal stenting.

Previous studies focus on morphological findings have suggested that there are a lot of serious ischemic injury on esophageal wall caused by the continuous radial force of the stent after esophageal stent implantation, which will stimulate the excessive proliferation of benign granulation tissue, leading to restenosis of the esophagus [8], [9]. In the proliferating granulation tissue, a large number of activated inflammatory cells are aggregated, which stimulates the activation, proliferation and secretion of a large amount of extracellular matrix of esophageal fibroblasts, and eventually leads to the formation of fibrous scars [10], [11], [12]. And the activation and proliferation of esophageal fibroblasts is considered to be the most important cellular activity leading to restenosis after esophageal stenting [13].

The transforming growth factor-β (TGFβ) is highly expressed in the response of wound healing by macrophage, and plays an important role in the process of fibrosis via inducing fibroblast differentiation into collagen-secreting fibroblasts [14]. Recent study demonstrated that the content of TGF-β1 in tissue microenvironment was significantly increased after skin trauma, which binds to the TGF-β receptor and promotes phosphorylation of R-Smads (Smad 2 and Smad3), activate gene transcription, promote proliferation, aggregation and secretion of extracellular matrix of skin fibroblasts, leading to skin scarring [15]. In addition, it has been reported that TGF-β plays an important role in the pathogenesis of eosinophilic esophagitis by enhancing fibroblast-specific gene expression and promoting fibroblast-mediated collagen-matrix contraction in eosinophilic esophagitis [16]. Therefore, the TGF-β1/Smads signaling pathway may play a key role in the formation of benign restenosis after esophageal stenting.

In this study, we analyzed the effect of the role and mechanism of TGF-β1/Smads signaling pathway in restenosis after esophageal stenting, and demonstrated that it is possible to control restenosis after esophageal stenting by inhibiting the TGF-β1/Smads signaling pathway. Therefore, it provides an effective idea and method for the prevention and treatment of restenosis after esophageal stent surgery.