Molecular hydrogen regulates PTEN-AKT-mTOR signaling via ROS to alleviate peritoneal dialysis-related peritoneal fibrosis.

Abstract

Peritoneal dialysis is used by approximately 11% of end-stage renal disease patients globally, yet prolonged use leads to peritoneal fibrosis. This study established a high-glucose-induced peritoneal fibrosis mouse model via intraperitoneal injection of high-glucose dialysate, followed by intervention with hydrogen-rich dialysate. Parallel in vitro experiments were conducted using MeT-5A mesothelial cells. Both in vivo and in vitro findings demonstrated that molecular hydrogen effectively suppressed the progression of high-glucose-induced peritoneal fibrosis. Mechanistically, hydrogen eliminated intracellular reactive oxygen species and blocked activation of the PTEN/AKT/mTOR signaling pathway. These results indicate that the ROS/PTEN/AKT/mTOR axis mediates the anti-fibrotic action of molecular hydrogen in the peritoneal environment.

Mechanism

Molecular hydrogen selectively scavenges intracellular ROS, thereby preventing activation of the PTEN/AKT/mTOR signaling cascade and inhibiting high-glucose-driven peritoneal fibrosis progression.