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CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism
  1. Annika Wilhelm1,
  2. Victoria Aldridge1,2,
  3. Debashis Haldar1,
  4. Amy J Naylor3,
  5. Christopher J Weston1,
  6. Abhilok Garg1,
  7. Janine Fear1,
  8. Gary M Reynolds1,
  9. Adam P Croft3,
  10. Neil C Henderson4,
  11. Christopher D Buckley3,
  12. Philip N Newsome1,2
  1. 1NIHR Birmingham Liver BRU and Centre for Liver Research, University of Birmingham, Birmingham, UK
  2. 2University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
  3. 3Centre for Translational Inflammation Research, University of Birmingham, Birmingham, West Midlands, UK
  4. 4MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
  1. Correspondence to Professor Philip Newsome, NIHR Birmingham Liver BRU and Centre for Liver Research, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK; P.N.Newsome{at}


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.


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