β-elemene alleviates esophageal fibrosis after endoscopic submucosal dissection via the FAP-mediated PTEN-PI3K/AKT signaling pathway

Abstract

Esophageal stricture caused by fibrosis is a serious complication after esophageal Endoscopic submucosal dissection (ESD). Myofibroblasts play a crucial role in esophageal fibrosis, so inhibiting activated myofibroblasts is a promising approach for treating esophageal fibrosis. β-Elemene, a natural product with anti-tumor and anti-fibrotic properties, has not been thoroughly examined in esophageal fibrosis. Additionally, fibroblast activation protein (FAP) and PTEN-PI3K/AKT signaling pathway are both notably linked to fibrotic diseases. Therefore, we investigated the potential mechanisms of β-elemene in esophageal fibrosis by treating primary human esophageal granulation fibroblasts (PHEGFs) with gradient concentrations of β-elemene. Our findings demonstrated that β-elemene inhibited the activity of PHEGFs in a dose-dependent manner, accompanied by downregulation of FAP, p-PI3K, and p-AKT protein expression, along with upregulation of p-PTEN protein expression. In addition, we substantiated the potential correlation between FAP and the PTEN-PI3K/AKT signaling pathway by establishing models of FAP overexpression and silencing. These results provide a new perspective on the potential mechanism of β-elemene in relieving esophageal fibrosis and offer novel therapeutic strategies for managing post-esophageal ESD stricture in clinical practice.

Keywords

• β-elemene
• Esophageal fibrosis
• PHEGFs
• FAP
• PTEN-PI3K/AKT