Article ; Online: Apamin suppresses biliary fibrosis and activation of hepatic stellate cells.
International journal of molecular medicine
2017 Volume 39, Issue 5, Page(s) 1188–1194
Abstract: ... we aimed to ascertain whether apamin inhibits biliary fibrosis and the proliferation of HSCs. Cholestatic ... epithelial cells (BECs) followed by fibrosis, cirrhosis and liver failure. Activated hepatic stellate cells (HSCs ... and portal fibroblasts are the major cellular effectors of enhanced collagen deposition in biliary ...
| Abstract | Cholestatic liver disease is characterized by the progressive destruction of biliary epithelial cells (BECs) followed by fibrosis, cirrhosis and liver failure. Activated hepatic stellate cells (HSCs) and portal fibroblasts are the major cellular effectors of enhanced collagen deposition in biliary fibrosis. Apamin, an 18 amino acid peptide neurotoxin found in apitoxin (bee venom), is known to block Ca2+-activated K+ channels and prevent carbon tetrachloride-induced liver fibrosis. In the present study, we aimed to ascertain whether apamin inhibits biliary fibrosis and the proliferation of HSCs. Cholestatic liver fibrosis was established in mouse models with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding. Cellular assays were performed on HSC-T6 cells (rat immortalized HSCs). DDC feeding led to increased hepatic damage and proinflammtory cytokine levels. Notably, apamin treatment resulted in decreased liver injury and proinflammatory cytokine levels. Moreover, apamin suppressed the deposition of collagen, proliferation of BECs and expression of fibrogenic genes in the DDC-fed mice. In HSCs, apamin suppressed activation of HSCs by inhibiting the Smad signaling pathway. These data suggest that apamin may be a potential therapeutic target in cholestatic liver disease. |
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| MeSH term(s) | Animals ; Apamin/pharmacology ; Biopsy ; Cell Proliferation/drug effects ; Cytokines/metabolism ; Diet ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Hepatic Stellate Cells/drug effects ; Hepatic Stellate Cells/metabolism ; Inflammation Mediators/metabolism ; Liver Cirrhosis, Biliary/etiology ; Liver Cirrhosis, Biliary/metabolism ; Liver Cirrhosis, Biliary/pathology ; Male ; Mice ; Signal Transduction/drug effects ; Smad Proteins/metabolism | |||||
| Chemical Substances | Cytokines ; Inflammation Mediators ; Smad Proteins ; Apamin (24345-16-2) | |||||
| Language | English | |||||
| Publishing date | 2017-05 | |||||
| Publishing country | Greece | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 1444428-8 | |||||
| ISSN | 1791-244X ; 1107-3756 | |||||
| ISSN (online) | 1791-244X | |||||
| ISSN | 1107-3756 | |||||
| DOI | 10.3892/ijmm.2017.2922 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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