Collagen VI as a driver and disease biomarker in human fibrosis

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 alpha 1, alpha 2 and alpha 3, which can be replaced with alternate chains of alpha 4, alpha 5 or alpha 6. The C-terminal globular domain (C5) of collagen VI alpha 3 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 C6M alpha 3 are emerging as important biomarkers for fibrotic conditions.

Automated summary

Fibrosis of visceral organs such as the lungs, heart, kidneys, and liver is a major cause of morbidity and mortality, and is also associated with other disorders like cancer and metabolic disease. Collagen VI, particularly in conditions like IPF and chronic liver and kidney diseases, has elevated expression and its chain fragments are emerging as important biomarkers for fibrotic conditions.