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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ecoenv.2024.117124 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Silica-mediated exacerbation of inflammatory arthritis: A novel murine model.
bioRxiv
January 2025
Department of Immunology and Microbiology, Scripps Research, La Jolla, San Diego, USA.
Objective: The mucosal origin hypothesis in rheumatoid arthritis (RA) posits that inhalant exposures, such as cigarette smoke and crystalline silica (c-silica), trigger immune responses contributing to disease onset. Despite the established risk posed by these exposures, the mechanistic link between inhalants, lung inflammation, and inflammatory arthritis remains poorly understood, partly from the lack of a suitable experimental model. As c-silica accelerates autoimmune phenotypes in lupus models and is a recognized risk factor for several autoimmune diseases, we investigated whether c-silica exposure could induce RA-like inflammatory arthritis in mice.
View Article and Find Full Text PDFHMGB1 mediates epithelial-mesenchymal transition and fibrosis in silicosis via RAGE/β-catenin signaling.
Chem Biol Interact
January 2025
Hebei Key Laboratory of Organ Fibrosis, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China. Electronic address:
Epithelial-mesenchymal transition (EMT) is implicated in the pathogenesis of silicosis. High mobility group box 1 (HMGB1) has been found to induce EMT in fibrotic diseases. Previous studies have revealed a critical role of HMGB1 in silicosis, whereas the detail mechanisms still obscure.
View Article and Find Full Text PDFCombined therapy with pirfenidone and nintedanib counteracts fibrotic silicosis in mice.
Br J Pharmacol
November 2024
State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Background And Purpose: Pneumoconiosis, especially silicosis, is a prevalent occupational disease with substantial global economic implications and lacks a definitive cure. Both pneumoconiosis and idiopathic pulmonary fibrosis (IPF) are interstitial lung diseases, which share many common physiological characteristics. Because pirfenidone and nintedanib are approved to treat IPF, their potential efficacy as antifibrotic agents in advanced silicosis deserves further exploration.
View Article and Find Full Text PDFPrimary hepatoid adenocarcinoma of the lung in patient with silicosis: a case report and literature review.
Front Oncol
October 2024
Department of Thoracic Surgery, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
Introduction: Hepatoid adenocarcinoma of the lung (HAL) is a special type of adenocarcinoma originating from the lung with adenoid- and hepatocyte-like differentiation. HAL is rare in clinical practice. Here, we present the case of a patient with HAL.
View Article and Find Full Text PDFTranscriptomic profiling of lung fibroblasts in silicosis: Regulatory roles of Nrf2 agonists in a mouse model.
Int Immunopharmacol
December 2024
Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address:
Silicosis is an occupational disease caused by long-term inhalation of free silica, resulting in a significant global health burden. Its pathogenesis remains unclear, and there is no effective treatment. Proliferative and activated myofibroblasts play a key role in the development of silicosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!