RT Journal Article SR Electronic T1 CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1175 OP 1185 DO 10.1136/gutjnl-2014-308325 VO 65 IS 7 A1 Annika Wilhelm A1 Victoria Aldridge A1 Debashis Haldar A1 Amy J Naylor A1 Christopher J Weston A1 Ditte Hedegaard A1 Abhilok Garg A1 Janine Fear A1 Gary M Reynolds A1 Adam P Croft A1 Neil C Henderson A1 Christopher D Buckley A1 Philip N Newsome YR 2016 UL http://gut.bmj.com/content/65/7/1175.abstract AB Introduction CD248 (endosialin) is a stromal cell marker expressed on fibroblasts and pericytes. During liver injury, myofibroblasts are the main source of fibrotic matrix.Objective To determine the role of CD248 in the development of liver fibrosis in the rodent and human setting.Design CD248 expression was studied by immunostaining and quantitative PCR in both normal and diseased human and murine liver tissue and isolated hepatic stellate cells (HSCs). Hepatic fibrosis was induced in CD248−/− and wild-type controls with carbon tetrachloride (CCl4) treatment.Results Expression of CD248 was seen in normal liver of humans and mice but was significantly increased in liver injury using both immunostaining and gene expression assays. CD248 was co-expressed with a range of fibroblast/HSC markers including desmin, vimentin and α-smooth muscle actin (α-SMA) in murine and human liver sections. CD248 expression was restricted to isolated primary murine and human HSC. Collagen deposition and α-SMA expression, but not inflammation and neoangiogenesis, was reduced in CD248−/− mice compared with wild-type mice after CCl4 treatment. Isolated HSC from wild-type and CD248−/− mice expressed platelet-derived growth factor receptor α (PDGFR-α) and PDGFR-β at similar levels. As expected, PDGF-BB stimulation induced proliferation of wild-type HSC, whereas CD248−/− HSC did not demonstrate a proliferative response to PDGF-BB. Abrogated PDGF signalling in CD248−/− HSC was confirmed by significantly reduced c-fos expression in CD248−/− HSC compared with wild-type HSC.Conclusions Our data show that deletion of CD248 reduces susceptibility to liver fibrosis via an effect on PDGF signalling, making it an attractive clinical target for the treatment of liver injury.