SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis

Varinder Athwal, James Pritchett, Jessica Llewellyn, Katherine Martin, Elizabeth Camacho, Sayyid Raza, Alexander Phythian-Adams, Lindsay Birchall, Aoibheann Mullan, Kimberley Su, Laurence Pearmain, Grace Dolman, Abed M. Zaitoun, Scott Friedman, Andrew MacDonald, William L. Irving, Indra N. Guha, Neil Hanley, Karen Piper Hanley

Research output: Contribution to journalArticlepeer-review


Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression towards cirrhosis. Inactivation of Sox9 in mice protected against both parenchymal and biliary fibrosis, improved liver function and ameliorated chronic inflammation. SOX9 was downstream of mechanosignaling factor, YAP1. These data demonstrate a role for SOX9 in liver fibrosis and open the way for the transcription factor and its dependent pathways as new diagnostic, prognostic and therapeutic targets in patients with liver fibrosis.
Original languageEnglish
JournalEMBO Molecular Medicine
Early online date6 Nov 2017
Publication statusPublished - 2017


  • SOX9
  • YAP1
  • Liver fibrosis
  • Extracellular matrix
  • hepatic stellate cells


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