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Updated: Jul 6, 2026
A Silicosis Mouse Model Established by Repeated Inhalation of Crystalline Silica Dust
Published on: January 6, 2023
LEF1 regulated CTHRC1 promotes silica-induced pulmonary fibrosis through CD44-dependent signaling.
Ting Wang1, Wenqing Sun2, Qingyan Yang3
1Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210000, China; Department of Occupational Medical and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
This study reveals the LEF1-CTHRC1-CD44 signaling axis drives silicosis, a fibrotic lung disease. Targeting CTHRC1 with liposomal siRNA shows therapeutic potential for treating lung fibrosis.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Molecular Biology
Background:
- Silicosis is an incurable fibrotic lung disease.
- Aberrant lung fibroblast activation is a hallmark of silicosis.
- CTHRC1 is a potential biomarker for fibroblast activation.
Purpose of the Study:
- To investigate the role of CTHRC1 in silicosis.
- To identify signaling pathways modulated by CTHRC1.
- To explore CTHRC1 as a therapeutic target for fibrotic lung diseases.
Main Methods:
- Transcriptomic analysis, LC-MS/MS, Co-immunoprecipitation, and nanoliposome techniques.
- In vitro fibroblast activation and in vivo mouse models of pulmonary fibrosis.
- RNA sequencing, Western blot, RT-qPCR, AlphaFold2, and rescue experiments.
Main Results:
- CTHRC1 is dysregulated in myogenesis and ECM pathways.
- LEF1 transcriptionally regulates CTHRC1, which binds CD44.
- The CTHRC1-CD44 complex signals through AKT, promoting fibrosis.
- Liposomal Cthrc1 siRNA reduced fibrosis in mouse models.
Conclusions:
- Identified the LEF1-CTHRC1-CD44 axis in silicosis pathogenesis.
- CTHRC1 mediates fibroblast-to-myofibroblast transition via CD44 and AKT signaling.
- CTHRC1 represents a promising therapeutic target for fibrotic lung diseases.
