H2 regulates PTEN-AKT-mTOR signaling to alleviate peritoneal fibrosisScientific Research


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

Authors:

Hongtao Lu, Wei Chen, Wenrui Liu, Yachen Si, Tingting Zhao, Xueli Lai, Zhimin Kang, Xuejun Sun, Zhiyong Guo

DOI: 10.1096/fj.201901981R

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Abstract:

As a convenient, effective and economical kidney replacement therapy for end-stage renal disease (ESRD), peritoneal dialysis is available in approximately 11% of ESRD patients worldwide. However, long-term peritoneal dialysis treatment causes peritoneal fibrosis. In recent years, the application potential of molecular hydrogen in the biomedicine has been well recognized. Molecular hydrogen selectively scavenges cytotoxic reactive oxygen species (ROS) and acts as an antioxidant. In this experiment, a high glucose-induced peritoneal fibrosis mouse model was successfully established by intraperitoneal injection of high glucose peritoneal dialysate, and peritoneal fibrosis mice were treated with hydrogen-rich peritoneal dialysate. In addition, in vitro studies of high glucose-induced peritoneal fibrosis were performed using MeT-5A cells. In vitro and in vivo experiments show that molecular hydrogen could inhibit peritoneal fibrosis progress induced by high glucose effectively. Furthermore, it has been found that molecular hydrogen alleviate fibrosis by eliminating intracellular ROS and inhibiting the activation of the PTEN/AKT/mTOR pathway. The present data proposes that molecular hydrogen exerts the capacity of anti-peritoneal fibrosis through the ROS/PTEN/AKT/mTOR pathway. Therefore, molecule hydrogen is a potential, safe, and effective treatment agent, with peritoneal protective property and great clinical significance.