Identifying collagen VI as a target of fibrotic diseases regulated by CREBBP/EP300
Year: 2020
Type: article
Abstract: Genomic analysis revealed that EP300 is highly enriched at enhancers associated with genes involved in multiple profibrotic pathways, and broad transcriptomic and proteomic profiling of CREBBP/EP300 inhibition by the chemical probe SGC-CBP30 identified collagen VI (Col VI) as a prominent downstream regulator of myofibroblast activity. Targeted Col VI knockdown results in significant decrease in profibrotic functions, including myofibroblast contractile force, extracellular matrix (ECM) production, chemotaxis, and wound healing. Further evidence for Col VI as a major determinant of fibrosis is its abundant expression within Dupuytren's nodules and also in the fibrotic foci of idiopathic pulmonary fibrosis (IPF). Thus, Col VI may represent a tractable therapeutic target across a range of fibrotic disorders.
Authors: Lynn M. Williams, Fiona E. McCann, Marisa A. Cabrita, Thomas Layton, Adam Cribbs, Bogdan Knezevic, Hai Fang, Julian Knight, Mingjun Zhang, Roman Fischer, Sarah Bonham, Leenart M. Steenbeek, Nan Yang, Manu Sood, Chris Bainbridge, David Warwick, Lorraine Harry, Dominique Davidson, Weilin Xie, Michael Sundstrӧm, Marc Feldmann, Jagdeep Nanchahal
Institutions: University of Oxford, Kennedy Institute of Rheumatology, National Institute for Health and Care Research, Centre for Human Genetics, National Health Service, Broomfield Hospital, Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust, Queen Victoria Hospital, Queen Victoria Hospital NHS Foundation Trust, St John's Hospital, Karolinska University Hospital
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Wellcome Trust
OpenAlex ID: W3047048129