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Updated: Sep 27, 2025
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Pyroptosis executor gasdermin D plays a key role in scleroderma and bleomycin-induced skin fibrosis
Huan Yang1, Yanqiang Shi1, Huiting Liu1
1Dermatology Hospital, Southern Medical University, Guangzhou, 510091, China.
Abstract:
The NLRP3 inflammasome and IL-1β are essential for scleroderma pathogenesis. Nevertheless, the role of pyroptosis executor gasdermin D(GSDMD), which is a downstream molecule of NLRP3 and is required for IL-1β release in some situations, has not yet been well elucidated in scleroderma. Here, we found that GSDMD was significantly up-regulated and activated in the skin of scleroderma patients and bleomycin-induced mouse model. What's more, the ablation of GSDMD ameliorates bleomycin-induced skin fibrosis according to HE staining, Masson staining and the detection of hydroxyproline contents. GSDMD deficiency also impaired macrophages infiltration and reduced inflammation response. Furthermore, the loss of GSDMD reduced Th17 differentiation in vivo and in vitro. Collectively, these findings provide the first demonstration that GSDMD related pyroptosis plays an important role in scleroderma pathogenesis.
Insights
Gasdermin D (GSDMD) pyroptosis is crucial in scleroderma. Inhibiting GSDMD reduces skin fibrosis and inflammation, highlighting its therapeutic potential for scleroderma treatment.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Scleroderma pathogenesis involves NLRP3 inflammasome and IL-1β.
- The role of gasdermin D (GSDMD), a pyroptosis executor, in scleroderma remains unclear.
Purpose of the Study:
- To investigate the role of GSDMD-mediated pyroptosis in scleroderma.
- To explore GSDMD as a potential therapeutic target for scleroderma.
Main Methods:
- Analysis of GSDMD expression in scleroderma patient skin and a bleomycin-induced mouse model.
- Assessment of skin fibrosis using HE staining, Masson staining, and hydroxyproline content.
- Evaluation of macrophage infiltration, inflammation, and Th17 differentiation in GSDMD-deficient models.
Main Results:
- GSDMD was significantly upregulated and activated in scleroderma skin.
- GSDMD ablation ameliorated bleomycin-induced skin fibrosis.
- GSDMD deficiency reduced macrophage infiltration, inflammation, and Th17 differentiation.
Conclusions:
- GSDMD-related pyroptosis plays a significant role in scleroderma pathogenesis.
- Targeting GSDMD may offer a novel therapeutic strategy for treating scleroderma.
