{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T08:53:40Z","timestamp":1762073620212,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forchungsgemeinschaft","doi-asserted-by":"publisher","award":["CH288\/6-2"],"award-info":[{"award-number":["CH288\/6-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Group VIA phospholipase A2 (iPLA2\u03b2) play diverse biological functions in epithelial cells and macrophages. Global deletion in iPLA2\u03b2-null (KO) mice leads to protection against hepatic steatosis in non-alcoholic fatty liver disease, in part, due to the replenishment of the loss of hepatocellular phospholipids. As the loss of phospholipids also occurs in hepatocellular carcinoma (HCC), we hypothesized that global deletion in KO mice may lead to protection against HCC. Here, HCC induced by diethylnitrosamine (DEN) was chosen because DEN causes direct injury to the hepatocytes. Male wild-type (WT) and KO mice at 3\u20135 weeks of age (12\u201313 mice\/group) were subjected to a single intraperitoneal treatment with 10 mg\/kg DEN, and mice were killed 12 months later. Analyses of histology, plasma cytokines, and gene expression were performed. Due to the low-dose DEN used, we observed a liver nodule in 3 of 13 WT and 2 of 12 KO mice. Only one DEN-treated WT mouse was confirmed to have HCC. DEN-treated KO mice did not show any HCC but showed suppressed hepatic expression of cell-cycle cyclinD2 and BCL2 as well as inflammatory markers IL-1\u03b2, IL-10, and VCAM-1. Notably, DEN-treated KO mice showed increased hepatic necrosis and elevated levels of plasma lactate dehydrogenase suggesting an exacerbation of liver injury. Thus, global iPLA2\u03b2 deficiency in DEN-treated mice rendered HCC protection by an induction of cell-cycle arrest. Our results suggest the role of iPLA2\u03b2 inhibition in HCC treatment.<\/jats:p>","DOI":"10.3390\/ijms232213760","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T02:44:32Z","timestamp":1667961872000},"page":"13760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["iPLA2\u03b2-Null Mice Show HCC Protection by an Induction of Cell-Cycle Arrest after Diethylnitrosamine Treatment"],"prefix":"10.3390","volume":"23","author":[{"given":"Adriana","family":"Andrade","sequence":"first","affiliation":[{"name":"Department of Internal Medicine IV (Gastroenterology and Infectious Disease), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Poth","sequence":"additional","affiliation":[{"name":"Center for Model System and Comparative Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Brobeil","sequence":"additional","affiliation":[{"name":"Tissuebank of the NCT, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1386-3350","authenticated-orcid":false,"given":"Uta","family":"Merle","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV (Gastroenterology and Infectious Disease), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-7664","authenticated-orcid":false,"given":"Walee","family":"Chamulitrat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV (Gastroenterology and Infectious Disease), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis","volume":"132","author":"Rudolph","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s11684-013-0256-4","article-title":"Inflammation and liver tumorigenesis","volume":"7","author":"Sun","year":"2013","journal-title":"Front. 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