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Potential Involvement of the IL-6/STAT3/MMP12 Signaling Axis in DMSO-Mediated Anti-Fibrotic Effects in Experimental
Yukang Zhu1, Lei Xu1, Wei You2
1Department of Nuclear Medicine, The First Hospital of Anhui University of Science and Technology; Anhui University of Science and Technology.
Abstract:
This study aims to investigate the anti-inflammatory and anti-fibrotic effects of dimethyl sulfoxide (DMSO) in a mouse model of silicosis, thereby exploring its potential therapeutic value. A mouse model of silicosis was established by intranasal instillation, and DMSO treatment was administered via intraperitoneal injection. The experiment was conducted over a period of 1 month. Lung tissues were collected from all mice; a subset was subjected to transcriptomic analysis, and differentially expressed genes were identified using the limma package. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted using ClusterProfiler to investigate gene functions and associated pathways. The remaining samples were subjected to histopathological assessment by hematoxylin and eosin staining (HE) and Masson's trichrome staining, while Western blot analysis was performed to validate transcriptomic results. This study suggests that DMSO may alleviate the fibrotic process in silicosis by modulating the IL-6/STAT3-MMP12 signaling axis. In the silica-induced silicosis mouse model, DMSO attenuated disease-associated weight loss and reduced collagen deposition. Transcriptomic analysis indicated that DMSO suppressed the activity of multiple fibrosis-related pathways and identified 51 key genes, including MMP12, which was significantly downregulated. Western blot analysis further confirmed reduced MMP12 expression, accompanied by markedly decreased levels of IL-6 and p-STAT3, suggesting the IL-6/STAT3 pathway may play a crucial role in regulating MMP12 expression. DMSO may attenuate inflammatory responses and pulmonary fibrosis in silicosis by inhibiting activation of the IL-6/STAT3 signaling pathway, thereby reducing MMP12 expression.
Insights
Dimethyl sulfoxide (DMSO) shows potential in treating silicosis by reducing lung inflammation and fibrosis. It works by inhibiting the IL-6/STAT3 pathway, which lowers MMP12 expression and alleviates disease symptoms in mice.
Area of Science:
- Pulmonary Medicine
- Toxicology
- Molecular Biology
Background:
- Silicosis is a serious lung disease caused by silica dust inhalation.
- Current treatments for silicosis are limited, highlighting the need for novel therapeutic strategies.
- Dimethyl sulfoxide (DMSO) has demonstrated anti-inflammatory properties in various contexts.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-fibrotic effects of DMSO in a mouse model of silicosis.
- To explore the potential therapeutic value of DMSO for silicosis treatment.
- To elucidate the molecular mechanisms underlying DMSO's effects on silicosis.
Main Methods:
- A mouse model of silicosis was established via intranasal instillation of silica.
- Mice were treated with DMSO via intraperitoneal injection for one month.
- Lung tissues underwent transcriptomic analysis (limma), GO/KEGG enrichment (ClusterProfiler), histopathology (HE, Masson's trichrome), and Western blot.
Main Results:
- DMSO treatment attenuated weight loss and reduced collagen deposition in silica-induced silicosis.
- Transcriptomic analysis revealed suppressed fibrosis-related pathways and identified 51 key genes, including downregulated MMP12.
- Western blot confirmed reduced MMP12, IL-6, and p-STAT3 levels, indicating inhibition of the IL-6/STAT3 signaling pathway.
Conclusions:
- DMSO alleviates pulmonary fibrosis in silicosis by modulating the IL-6/STAT3-MMP12 signaling axis.
- DMSO demonstrates therapeutic potential for silicosis by inhibiting inflammation and fibrosis.
- Targeting the IL-6/STAT3 pathway represents a promising therapeutic strategy for silicosis.
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