Glycyrrhetinic Acid Mitigates Radiation- Induced Pulmonary Fibrosis via Inhibiting the Secretion of TGF-b1 by Treg Cells

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a common side effect of radiation therapy for thoracic tumors with-out effective prevention and treatment methods at present. The aim of this study was to explore whether glycyrrhetinic acid (GA) has a protective effect on RIPF and the underlying mechanism.Methods and Materials: A RIPF mouse model administered GA was used to determine the effect of GA on RIPF. The cocul-tivation of regulatory T (Treg) cells with mouse lung epithelial-12 cells or mouse embryonic fibroblasts and intervention with GA or transforming growth factor -01 (TGF-01) inhibitor to block TGF-01 was conducted to study the mechanism by which GA alleviates RIPF. Furthermore, injection of Treg cells into GA-treated RIPF mice to upregulate TGF-01 levels was performed to verify the roles of TGF-01 and Treg cells. Results: GA intervention improved the damage to lung tissue structure and collagen deposition and inhibited Treg cell infiltra-tion, TGF-01 levels, epithelial mesenchymal transition (EMT), and myofibroblast (MFB) transformation in mice after irradia-tion. Treg cell-induced EMT and MFB transformation in vitro were prevented by GA, as well as a TGF-01 inhibitor, by decreasing TGF-01. Furthermore, reinfusion of Treg cells upregulated TGF-01 levels and exacerbated RIPF in GA-treated RIPF mice.Conclusions: GA can improve RIPF in mice, and the corresponding mechanisms may be related to the inhibition of TGF-01 secreted by Treg cells to induce EMT and MFB transformation. Therefore, GA may be a promising therapeutic candidate for the clinical treatment of RIPF. (c) 2023 Elsevier Inc. All rights reserved.