1. Academic Validation
  2. Apamin suppresses biliary fibrosis and activation of hepatic stellate cells

Apamin suppresses biliary fibrosis and activation of hepatic stellate cells

  • Int J Mol Med. 2017 May;39(5):1188-1194. doi: 10.3892/ijmm.2017.2922.
Jung-Yeon Kim 1 Hyun-Jin An 1 Woon-Hae Kim 1 Yoon-Yub Park 2 Kyung Duck Park 3 Kwan-Kyu Park 1
Affiliations

Affiliations

  • 1 Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
  • 2 Department of Physiology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
  • 3 Department of Dermatology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
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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