Open Access

Apamin suppresses biliary fibrosis and activation of hepatic stellate cells

  • Authors:
    • Jung-Yeon Kim
    • Hyun-Jin An
    • Woon-Hae Kim
    • Yoon-Yub Park
    • Kyung Duck Park
    • Kwan-Kyu Park
  • View Affiliations

  • Published online on: March 17, 2017     https://doi.org/10.3892/ijmm.2017.2922
  • Pages: 1188-1194
  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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May-2017
Volume 39 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kim J, An H, Kim W, Park Y, Park KD and Park K: Apamin suppresses biliary fibrosis and activation of hepatic stellate cells. Int J Mol Med 39: 1188-1194, 2017.
APA
Kim, J., An, H., Kim, W., Park, Y., Park, K.D., & Park, K. (2017). Apamin suppresses biliary fibrosis and activation of hepatic stellate cells. International Journal of Molecular Medicine, 39, 1188-1194. https://doi.org/10.3892/ijmm.2017.2922
MLA
Kim, J., An, H., Kim, W., Park, Y., Park, K. D., Park, K."Apamin suppresses biliary fibrosis and activation of hepatic stellate cells". International Journal of Molecular Medicine 39.5 (2017): 1188-1194.
Chicago
Kim, J., An, H., Kim, W., Park, Y., Park, K. D., Park, K."Apamin suppresses biliary fibrosis and activation of hepatic stellate cells". International Journal of Molecular Medicine 39, no. 5 (2017): 1188-1194. https://doi.org/10.3892/ijmm.2017.2922