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Journal article : Review

Collagen VI as a driver and disease biomarker in human fibrosis

Abstract:
Fibrosis of visceral organs such as the lungs, heart, kidneys and liver remains a major cause of morbidity and mortality and is also associated with many other disorders, including cancer and metabolic disease. In this review, we focus upon the microfibrillar collagen VI, which is present in the extracellular matrix (ECM) of most tissues. However, expression is elevated in numerous fibrotic conditions, such as idiopathic pulmonary disease (IPF), and chronic liver and kidney diseases. Collagen VI is composed of three subunits α1, α2 and α3, which can be replaced with alternate chains of α4, α5 or α6. The C-terminal globular domain (C5) of collagen VI α3 can be proteolytically cleaved to form a biologically active fragment termed endotrophin, which has been shown to actively drive fibrosis, inflammation and insulin resistance. Tissue biopsies have long been considered the gold standard for diagnosis and monitoring of progression of fibrotic disease. The identification of neoantigens from enzymatically processed collagen chains have revolutionised the biomarker field, allowing rapid diagnosis and evaluation of prognosis of numerous fibrotic conditions, as well as providing valuable clinical trial endpoint determinants. Collagen VI chain fragments such as endotrophin (PRO-C6), C6M and C6Mα3 are emerging as important biomarkers for fibrotic conditions.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1111/febs.16039

Authors


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Role:
Author
ORCID:
0000-0002-3092-0049
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Kennedy Institute for Rheumatology
Role:
Author
ORCID:
0000-0002-1610-5240
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Kennedy Institute for Rheumatology
Oxford college:
Wolfson College
Role:
Author
ORCID:
0000-0002-9579-9411


Publisher:
FEBS Press
Journal:
The FEBS Journal More from this journal
Volume:
289
Issue:
13
Pages:
3603-3629
Place of publication:
England
Publication date:
2021-06-14
Acceptance date:
2021-05-27
DOI:
EISSN:
1742-4658
ISSN:
1742-464X
Pmid:
34109754


Language:
English
Keywords:
Subtype:
Review
Pubs id:
1182647
Local pid:
pubs:1182647
Deposit date:
2022-03-16

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