Related Experiment Video
Updated: Mar 15, 2026
Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition
Published on: March 3, 2023
Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species-Induced Mouse Model
Florence Morin1,2, Niloufar Kavian1,2, Carole Nicco1
1Institut Cochin, INSERM U1016, CNRS, UMR8104, Université Paris Descartes, Université Sorbonne Paris Cité, 75014 Paris, France; and.
Abstract:
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy, and immunological abnormalities. Recent insights on the implication of STAT3, AKT, and Wnt/β-catenin in fibrosis have prompted us to investigate, in a mouse model of ROS-induced SSc, the effects of niclosamide, an antihelmintic drug that inhibits both of these signaling pathways. SSc was induced in BALB/c mice by daily s.c. injections of hypochlorous acid (HOCl). Mice were treated or not every other day, 5 d a week, for 6 wk, by niclosamide. Skin and lung fibrosis as well as immunological features were studied. Mice exposed to HOCl developed a diffuse cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase 1 autoantibodies. STAT3, AKT, and Wnt/β-catenin pathways were hyperactivated in the skin and the lungs of diseased mice. Niclosamide reversed fibrosis of the skin and the lungs. Beneficial immunological effects were also observed because niclosamide decreased the activation of CD4+ and CD8+ T cells, autoimmune B cell activation, as well as IL-4 and IL-13 production in the skin. The improvement permitted by niclosamide in the mouse model of HOCl-induced SSc as well as the well-documented safety profile of this drug provide a rationale for the evaluation of niclosamide in the management of patients affected by this disease.
Insights
Niclosamide, an antihelminthic drug, effectively reversed skin and lung fibrosis in a mouse model of Systemic Sclerosis (SSc). It also improved immune responses, suggesting potential for SSc patient treatment.
Area of Science:
- Immunology
- Rheumatology
- Pharmacology
Background:
- Systemic sclerosis (SSc) is a fibrotic connective tissue disease with vasculopathy and immune abnormalities.
- STAT3, AKT, and Wnt/β-catenin pathways are implicated in SSc fibrosis.
- A mouse model of ROS-induced SSc was established using hypochlorous acid (HOCl).
Purpose of the Study:
- To investigate the therapeutic effects of niclosamide in a mouse model of Systemic Sclerosis.
- To assess niclosamide's impact on fibrosis and immunological features in SSc.
- To evaluate the role of STAT3, AKT, and Wnt/β-catenin pathways in SSc pathogenesis and niclosamide's inhibitory effects.
Main Methods:
- BALB/c mice were induced with SSc using daily hypochlorous acid (HOCl) injections.
- Mice were treated with niclosamide every other day for 6 weeks.
- Skin and lung fibrosis, immunological markers, and specific signaling pathways were analyzed.
Main Results:
- HOCl-induced SSc mice exhibited skin/lung fibrosis, autoantibodies, and hyperactivated STAT3, AKT, and Wnt/β-catenin pathways.
- Niclosamide treatment significantly reversed skin and lung fibrosis.
- Niclosamide reduced T cell activation, B cell activation, and IL-4/IL-13 production, indicating beneficial immunological effects.
Conclusions:
- Niclosamide demonstrates significant therapeutic potential in ameliorating fibrosis and immune dysregulation in an SSc mouse model.
- The drug's inhibitory effects on STAT3, AKT, and Wnt/β-catenin pathways contribute to its beneficial actions in SSc.
- Given its safety profile, niclosamide warrants clinical evaluation for managing Systemic Sclerosis patients.
