{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:15:25Z","timestamp":1789748125945,"version":"4.0.1"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T00:00:00Z","timestamp":1492041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Transforming growth factor (TGF)-\u03b21 plays a crucial role in the epithelial-to-mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC), which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a major component of bee venom and is effective in rheumatoid arthritis, pain relief, cancer cell proliferation, fibrosis and immune modulating activity. In this study, we found that MEL inhibits hepatic EMT in vitro and in vivo, regulating the TGF\u03b2\/Smad and TGF\u03b2\/nonSmad signaling pathways. MEL significantly inhibited TGF-\u03b21-induced expression of EMT markers (E-cadherin reduction and vimentin induction) in vitro. These results were confirmed in CCl4-induced liver in vivo. Treatment with MEL almost completely blocked the phosphorylation of Smad2\/3, translocation of Smad4 and phosphorylation of JNK in vitro and in vivo. Taken together, these results suggest that MEL suppresses EMT by inhibiting the TGF\u03b2\/Smad and TGF\u03b2\/nonSmad-c-Jun N-terminal kinase (JNK)\/Mitogen-activated protein kinase (MAPK) signaling pathways. These results indicated that MEL possesses potent anti-fibrotic and anti-EMT properties, which may be responsible for its effects on liver diseases.<\/jats:p>","DOI":"10.3390\/toxins9040138","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T10:55:44Z","timestamp":1492080944000},"page":"138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Suppression of Hepatic Epithelial-to-Mesenchymal Transition by Melittin via Blocking of TGF\u03b2\/Smad and MAPK-JNK Signaling Pathways"],"prefix":"10.3390","volume":"9","author":[{"given":"Ji-Hyun","family":"Park","sequence":"first","affiliation":[{"name":"College of Pharmacy, Keimyung University, Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoungduck","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Keimyung University, Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan-Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, Daegu Catholic University Medical Center, Duryugongwon-ro, Nam-gu, Daegu 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/hep.23765","article-title":"Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes","volume":"52","author":"Kaimori","year":"2010","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1582-4934.2006.tb00292.x","article-title":"Modern pathogenetic concepts of liver fibrosis suggest stellate cells and tgf-beta as major players and therapeutic targets","volume":"10","author":"Gressner","year":"2006","journal-title":"J. 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