SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis
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 d...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Wiley Open Access
2017
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| Online Access: | https://eprints.nottingham.ac.uk/46609/ |
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| author | Athwal, Varinder S. Pritchett, James Llewellyn, Jessica Martin, Katherine Camacho, Elizabeth Raza, Sayyid M.A. Phythian-Adams, Alexander Birchall, Lindsay J. Mullan, Aoibheann F. Su, Kim Pearmain, Laurence Dolman, Grace Zaitoun, Abed M. Friedman, Scott L. MacDonald, Andrew Irving, William L. Guha, Indra N. Hanley, Neil A. Hanley, Karen Piper |
| author_facet | Athwal, Varinder S. Pritchett, James Llewellyn, Jessica Martin, Katherine Camacho, Elizabeth Raza, Sayyid M.A. Phythian-Adams, Alexander Birchall, Lindsay J. Mullan, Aoibheann F. Su, Kim Pearmain, Laurence Dolman, Grace Zaitoun, Abed M. Friedman, Scott L. MacDonald, Andrew Irving, William L. Guha, Indra N. Hanley, Neil A. Hanley, Karen Piper |
| author_sort | Athwal, Varinder S. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:02:44Z |
| format | Article |
| id | nottingham-46609 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:02:44Z |
| publishDate | 2017 |
| publisher | Wiley Open Access |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-466092020-05-04T19:16:10Z https://eprints.nottingham.ac.uk/46609/ SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis Athwal, Varinder S. Pritchett, James Llewellyn, Jessica Martin, Katherine Camacho, Elizabeth Raza, Sayyid M.A. Phythian-Adams, Alexander Birchall, Lindsay J. Mullan, Aoibheann F. Su, Kim Pearmain, Laurence Dolman, Grace Zaitoun, Abed M. Friedman, Scott L. MacDonald, Andrew Irving, William L. Guha, Indra N. Hanley, Neil A. Hanley, Karen Piper 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. Wiley Open Access 2017-11-06 Article PeerReviewed Athwal, Varinder S., Pritchett, James, Llewellyn, Jessica, Martin, Katherine, Camacho, Elizabeth, Raza, Sayyid M.A., Phythian-Adams, Alexander, Birchall, Lindsay J., Mullan, Aoibheann F., Su, Kim, Pearmain, Laurence, Dolman, Grace, Zaitoun, Abed M., Friedman, Scott L., MacDonald, Andrew, Irving, William L., Guha, Indra N., Hanley, Neil A. and Hanley, Karen Piper (2017) SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis. EMBO Molecular Medicine, 9 (12). pp. 1696-1710. ISSN 1757-4684 SOX9; YAP1; Liver fibrosis; Extracellular matrix; Hepatic stellate cells http://embomolmed.embopress.org/content/early/2017/11/06/emmm.201707860 doi:10.15252/emmm.201707860 doi:10.15252/emmm.201707860 |
| spellingShingle | SOX9; YAP1; Liver fibrosis; Extracellular matrix; Hepatic stellate cells Athwal, Varinder S. Pritchett, James Llewellyn, Jessica Martin, Katherine Camacho, Elizabeth Raza, Sayyid M.A. Phythian-Adams, Alexander Birchall, Lindsay J. Mullan, Aoibheann F. Su, Kim Pearmain, Laurence Dolman, Grace Zaitoun, Abed M. Friedman, Scott L. MacDonald, Andrew Irving, William L. Guha, Indra N. Hanley, Neil A. Hanley, Karen Piper SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis |
| title | SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis |
| title_full | SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis |
| title_fullStr | SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis |
| title_full_unstemmed | SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis |
| title_short | SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis |
| title_sort | sox9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis |
| topic | SOX9; YAP1; Liver fibrosis; Extracellular matrix; Hepatic stellate cells |
| url | https://eprints.nottingham.ac.uk/46609/ https://eprints.nottingham.ac.uk/46609/ https://eprints.nottingham.ac.uk/46609/ |