GAMG ameliorates silica-induced pulmonary inflammation and fibrosis via the regulation of EMT and NLRP3/TGF-β1/Smad signaling pathway
Jing Zhang, Jing Zhang, Jiazhen Zhang, Jiazhen Zhang, Zongze Yao, Wei Shao, Yuanchao Song, Wenjian Tang, Bo Li
Abstract
Silicosis is an occupational disease caused by exposure to silica characterized by pulmonary inflammation and fibrosis, for which there is a lack of effective drugs. Glycyrrhetinic acid 3-O-β-D-glucuronide (GAMG) can treat silicosis due to its anti-inflammatory and anti-fibrotic properties. Here, the effect of therapeutic interventions of GAMG was evaluated in early-stage and advanced silicosis mouse models. GAMG significantly improved fibrotic pathological changes and collagen deposition in the lungs, alleviated lung inflammation in the BALF, reduced the expression of TNF-α, IL-6, NLRP3, TGF-β1, vimentin, Col-Ⅰ, N-cadherin, and inhibited epithelial-mesenchymal transition (EMT), thereby ameliorating pulmonary fibrosis. Moreover, the dose of 100 mg/kg GAMG can effectively prevent early-stage silicosis, while that of 200 mg/kg was recommended for advanced silicosis. In vitro and in vivo study verified that GAMG can suppress EMT through the NLRP3/TGF-β1/Smad2/3 signaling pathway. Therefore, GAMG could be a promising preventive (early-stage silicosis) and therapeutic (advanced silicosis) strategy, which provides a new idea for formulating prevention and treatment strategies.