- 作者: Yu-An Hsu, Ching-Yao Chang, Joung-Liang Lan, Ju-Pi Li, Hui-Ju Lin, Chih-Sheng Chen, Lei Wan and Fu-Tong Liu
- 作者服務機構: 1. School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 40402, Taiwan 2. Department of Biotechnology, Asia University, Taichung, 40402, Taiwan 3. Rheumatology Research Center, China Medical University Hospital, Taichung, 40402, Taiwan 4. School of Medicine, China Medical University, Taichung, 40402, Taiwan 5. Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, 40402, Taiwan 6. School of Medicine, China Medical University, Taichung, 40402, Taiwan 7. Department of Ophthalmology, China Medical University Hospital, Taichung, 40402, Taiwan 8. Division of Chinese Traumatology, China Medical University Hospital, Taichung, 40402, Taiwan 9. Division of Chinese Medicine, Asia University Hospital, Taichung, 40402, Taiwan 10. Department of Biotechnology, Asia University, Taichung, 40402, Taiwan 11. Department of Gynecology, China Medical University Hospital, Taichung, 40402, Taiwan 12. Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan 13. Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, CA, 95816, USA
- 中文摘要:
- 英文摘要:
Background
Galectin-9 is a β-galactoside-binding protein with two carbohydrate recognition domains. Recent studies have revealed that galectin-9 regulates cellular biological reactions and plays a pivotal role in fibrosis. The aim of this study was to determine the role of galectin-9 in the pathogenesis of bleomycin-induced systemic sclerosis (SSc).
Methods
Human galectin-9 levels in the serum of patients with SSc and mouse sera galectin-9 levels were measured by a Bio-Plex immunoassay and enzyme-linked immunosorbent assay. Lung fibrosis was induced using bleomycin in galectin-9 wild-type and knockout mice. The effects of galectin-9 on the fibrosis markers and signaling molecules in the mouse lung tissues and primary lung fibroblast cells were assessed with western blotting and quantitative polymerase chain reaction.
Results
Galectin-9 levels in the serum were significantly higher (9-fold) in patients compared to those of healthy individuals. Galectin-9 deficiency in mice prominently ameliorated epithelial proliferation, collagen I accumulation, and α-smooth muscle actin expression. In addition, the galectin-9 knockout mice showed reduced protein expression levels of fibrosis markers such as Smad2/3, connective tissue growth factor, and endothelin-1. Differences between the wild-type and knockout groups were also observed in the AKT, mitogen-activated protein kinase, and c-Jun N-terminal kinase signaling pathways. Galectin-9 deficiency decreased the signal activation induced by transforming growth factor-beta in mouse primary fibroblasts, which plays a critical role in fibroblast activation and aberrant catabolism of the extracellular matrix.
Conclusions
Our findings suggest that lack of galectin-9 protects against bleomycin-induced SSc. Moreover, galectin-9 might be involved in regulating the progression of fibrosis in multiple pathways. - 中文關鍵字:
- 英文關鍵字: Galectin-9, Bleomycin, TGF-β, Fibrosis, Systemic sclerosis