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

Research output: Contribution to journalReviewResearchpeer-review

  • Martin Pehrsson
  • Joachim Hog Mortensen
  • Tina Manon-Jensen
  • Anne-Christine Bay-Jensen
  • Morten Asser Karsdal
  • Davies, Michael Jonathan

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.

Original languageEnglish
JournalExpert Review of Molecular Diagnostics
Volume21
Issue number10
Pages (from-to)1049-1064
ISSN1473-7159
DOIs
Publication statusPublished - 2021

    Research areas

  • Collagen cross-linking, lysyl oxidase, transglutaminse 2, peroxidasin, organ fibrosis, fibrosis resolution, cross-linking biomarkers, LYSYL HYDROXYLASE 3, EXTRACELLULAR TRANSGLUTAMINASE 2, IDIOPATHIC PULMONARY-FIBROSIS, BONE MORPHOGENETIC PROTEIN-1, CAUSES HYPERELASTOSIS CUTIS, GLYCATION END-PRODUCTS, GROWTH-FACTOR-BETA, TISSUE TRANSGLUTAMINASE, TERMINAL PROPEPTIDE, INTESTINAL FIBROSIS

ID: 286863694