TY - JOUR

T1 - Enzymatic cross-linking of collagens in organ fibrosis - resolution and assessment

AU - Pehrsson, Martin

AU - Mortensen, Joachim Hog

AU - Manon-Jensen, Tina

AU - Bay-Jensen, Anne-Christine

AU - Karsdal, Morten Asser

AU - Davies, Michael Jonathan

PY - 2021

Y1 - 2021

N2 - Introduction: Enzymatic cross-linking of the collagens within the extracellular matrix (ECM) catalyzed by enzymes such as lysyl oxidase (LOX) and lysyl oxidase like-enzymes 1-4 (LOXL), transglutaminase 2 (TG2), and peroxidasin (PXDN) contribute to fibrosis progression through extensive collagen cross-linking. Studies in recent years have begun elucidating the important role of collagen cross-linking in perpetuating progression of organ fibrosis independently of inflammation through an increasingly stiff and noncompliant ECM. Therefore, collagen cross-linking and the cross-linking enzymes have become new targets in anti-fibrotic therapy as well as targets of novel biomarkers to properly assess resolution of the fibrotic ECM. Areas covered: The enzymatic actions of enzymes catalyzing collagen cross-linking and their relevance in organ fibrosis. Potential biomarkers specifically quantifying proteolytic fragments of collagen cross-linking is discussed based on Pubmed search done in November 2020 as well as the authors knowledge. Expert opinion: Current methods for the assessment of fibrosis involve the use of invasive and/or cumbersome and expensive methods such as tissue biopsies. Thus, an unmet need exists for the development and validation of minimally invasive biomarkers of proteolytic fragments of cross-linked collagens. These biomarkers may aid in the development and proper assessment of fibrosis resolution in coming years.

AB - Introduction: Enzymatic cross-linking of the collagens within the extracellular matrix (ECM) catalyzed by enzymes such as lysyl oxidase (LOX) and lysyl oxidase like-enzymes 1-4 (LOXL), transglutaminase 2 (TG2), and peroxidasin (PXDN) contribute to fibrosis progression through extensive collagen cross-linking. Studies in recent years have begun elucidating the important role of collagen cross-linking in perpetuating progression of organ fibrosis independently of inflammation through an increasingly stiff and noncompliant ECM. Therefore, collagen cross-linking and the cross-linking enzymes have become new targets in anti-fibrotic therapy as well as targets of novel biomarkers to properly assess resolution of the fibrotic ECM. Areas covered: The enzymatic actions of enzymes catalyzing collagen cross-linking and their relevance in organ fibrosis. Potential biomarkers specifically quantifying proteolytic fragments of collagen cross-linking is discussed based on Pubmed search done in November 2020 as well as the authors knowledge. Expert opinion: Current methods for the assessment of fibrosis involve the use of invasive and/or cumbersome and expensive methods such as tissue biopsies. Thus, an unmet need exists for the development and validation of minimally invasive biomarkers of proteolytic fragments of cross-linked collagens. These biomarkers may aid in the development and proper assessment of fibrosis resolution in coming years.

KW - Collagen cross-linking

KW - lysyl oxidase

KW - transglutaminse 2

KW - peroxidasin

KW - organ fibrosis

KW - fibrosis resolution

KW - cross-linking biomarkers

KW - LYSYL HYDROXYLASE 3

KW - EXTRACELLULAR TRANSGLUTAMINASE 2

KW - IDIOPATHIC PULMONARY-FIBROSIS

KW - BONE MORPHOGENETIC PROTEIN-1

KW - CAUSES HYPERELASTOSIS CUTIS

KW - GLYCATION END-PRODUCTS

KW - GROWTH-FACTOR-BETA

KW - TISSUE TRANSGLUTAMINASE

KW - TERMINAL PROPEPTIDE

KW - INTESTINAL FIBROSIS

U2 - 10.1080/14737159.2021.1962711

DO - 10.1080/14737159.2021.1962711

M3 - Review

C2 - 34330194

VL - 21

SP - 1049

EP - 1064

JO - Expert Review of Molecular Diagnostics

JF - Expert Review of Molecular Diagnostics

SN - 1473-7159

IS - 10

ER -