{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:04:18Z","timestamp":1772168658261,"version":"3.50.1"},"reference-count":76,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":503,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA085862"],"award-info":[{"award-number":["CA085862"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cancer Research Institute\/ Fibrolamellar Cancer Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000009","name":"NIH","doi-asserted-by":"publisher","award":["T32HL07899"],"award-info":[{"award-number":["T32HL07899"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Fibrolamellar Carcinoma (FLC) is a rare liver cancer that affects adolescents and young adults. Genomic analysis in FLC has revealed a 400 kB deletion in chromosome 19 that leads to a fusion protein, DNAJB1-PRKACA (DnaJ-PKAc) comprised of the first exon of the heat shock protein 40 (DNAJB1) and exons 2\u201310 of the catalytic subunit of protein kinase A (PRKACA). Here, we report a new zebrafish model of FLC induced by ectopic expression of zebrafish DnaJa-Pkaca (zfDnaJ-Pkaca) in hepatocytes that is amenable to live imaging of early innate immune inflammation. Expression of zfDnaJ-Pkaca in hepatocytes induces hepatomegaly and increased hepatocyte size. In addition, FLC larvae exhibit early innate immune inflammation characterized by early infiltration of neutrophils and macrophages into the liver microenvironment. Increased caspase-a activity was also found in the liver of FLC larvae, and pharmacological inhibition of TNF\u03b1 and caspase-a decreased liver size and inflammation. Overall, these findings show that innate immune inflammation is an early feature in a zebrafish model of FLC and that that pharmacological inhibition of TNF\u03b1 or caspase-1 activity might be targets to treat inflammation and progression in FLC.<\/jats:p>","DOI":"10.1242\/dmm.042564","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T15:25:13Z","timestamp":1582730713000},"source":"Crossref","is-referenced-by-count":7,"title":["DnaJ-PKAc fusion induces liver inflammation in a zebrafish model of Fibrolamellar Carcinoma"],"prefix":"10.1242","author":[{"given":"Sofia","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8209-372X","authenticated-orcid":false,"given":"Ruth A.","family":"Houseright","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin G.","family":"Korte","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7940-6254","authenticated-orcid":false,"given":"Anna","family":"Huttenlocher","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, USA"},{"name":"Department of Pediatrics, University of Wisconsin-Madison, Madison, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042623433220100_DMM042564C1","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1177\/1753425912441956","article-title":"Evolution of inflammasome functions in vertebrates: inflammasome and caspase-1 trigger fish macrophage cell death but are dispensable for the processing of IL-1\u03b2","volume":"18","author":"Angosto","year":"2012","journal-title":"Innate Immun."},{"key":"2021042623433220100_DMM042564C2","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.tips.2004.06.008","article-title":"PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease","volume":"25","author":"Banner","year":"2004","journal-title":"Trends Pharmacol. 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