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Immunol."],"abstract":"<jats:p>During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory\/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1277808","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:57Z","timestamp":1701734457000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":53,"title":["Macrophages and platelets in liver fibrosis and hepatocellular carcinoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Martina","family":"Casari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Siegl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Deppermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Schuppan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0396.2007.00752.x","article-title":"Liver lipid metabolism","volume":"92","author":"Nguyen","year":"2008","journal-title":"J Anim Physiol Anim Nutr (Berl)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.09.019","article-title":"The liver","volume":"27","author":"Trefts","year":"2017","journal-title":"Curr Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2015.122","article-title":"Regulation of glucose metabolism from a liver-centric perspective","volume":"48","author":"Han","year":"2016","journal-title":"Exp Mol Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1021\/tx500444e","article-title":"Survey of human oxidoreductases and cytochrome P450 enzymes involved in the metabolism of xenobiotic and natural chemicals","volume":"28","author":"Rendic","year":"2015","journal-title":"Chem Res Toxicol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.3","article-title":"Liver immunology and its role in inflammation and homeostasis","volume":"13","author":"Robinson","year":"2016","journal-title":"Cell Mol Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2074-7_23","article-title":"Measurement of blood coagulation factor synthesis in cultures of human hepatocytes","volume":"1250","author":"Heinz","year":"2015","journal-title":"Methods Mol Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12772","article-title":"Thrombopoietin from beginning to end","volume":"165","author":"Hitchcock","year":"2014","journal-title":"Br J Haematol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"10.15761\/JTS.1000182","DOI":"10.15761\/JTS.1000182","article-title":"Hemostasis, bleeding and thrombosis in liver disease","volume":"3","author":"Flores","year":"2017","journal-title":"J Transl Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.04.016","article-title":"Bleeding and thrombotic complications in patients with cirrhosis: A state-of-the-art appraisal","volume":"21","author":"Rautou","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.3390\/jcm9082648","article-title":"Liver steatosis, gut-liver axis, microbiome and environmental factors. 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