Selective activation of Toll-like receptor 7 in activated hepatic stellate cells may modulate their profibrogenic phenotype
| Autor: | Ying-Hsien Huang, Po-Chin Tsai, Ming-Huei Chou, Tsun-Mei Lin, Chih-Sung Hsieh, Jiin-Haur Chuang, Yung-Ying Du |
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| Rok vydání: | 2012 |
| Předmět: |
Liver Cirrhosis
Male Gene Expression Biology Biochemistry Collagen Type I Cell Line Small hairpin RNA Rats Sprague-Dawley Cell Movement medicine Hepatic Stellate Cells Gene silencing Animals RNA Small Interfering Receptor Molecular Biology Cell Proliferation Liver injury Toll-like receptor Monocyte virus diseases Cell migration Cell Biology medicine.disease Actins Cell biology Rats Jaundice Obstructive Thiazoles medicine.anatomical_structure Phenotype Toll-Like Receptor 7 Immunology Hepatic stellate cell Quinolines |
| Zdroj: | The Biochemical journal. 447(1) |
| ISSN: | 1470-8728 |
| Popis: | Cholestatic liver injury may activate HSCs (hepatic stellate cells) to a profibrogenic phenotype, contributing to liver fibrogenesis. We have previously demonstrated the involvement of TLR (Toll-like receptor) 7 in the pathogenesis of biliary atresia. In the present study we investigated the ability of TLR7 to modulate the profibrogenic phenotype in HSCs. Obstructive jaundice was associated with significant down-regulation of TLR7. Primary HSCs isolated from BDL (bile duct ligation) rats with obstructive jaundice exhibited reduced expression of TLR7 and increased expression of α-SMA (α-smooth muscle actin) and collagen-α1 compared with sham rats, reflecting HSC-mediated changes. Treatment of primary activated rat HSCs and rat T6 cells with CL075, a TLR7 and TLR8 ligand, significantly decreased expression of MCP-1 (monocyte chemotactic protein-1), TGF-β1 (transforming growth factor-β1), collagen-α1 and MMP-2 (matrix metalloproteinase-2), and inhibited cell proliferation and migration. In contrast, silencing TLR7 expression with shRNA (short hairpin RNA) in T6 cells effectively blocked the effects of CL075 stimulation, reversing the changes in MCP-1, TGF-β1 and collagen-α1 expression and accelerating cell migration. Our results indicate that obstructive jaundice is associated with down-regulation of TLR7 and up-regulation of profibrogenic gene expression in HSCs. Selective activation of TLR7 may modulate the profibrogenic phenotype in activated HSCs associated with cholestatic liver injury. |
| Databáze: | OpenAIRE |
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