ABSTRACT

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.

摘要

简介: 细胞外基质 (ECM) 内胶原蛋白的酶促交联由赖氨酰氧化酶 (LOX) 和赖氨酰氧化酶样酶 1-4 (LOXL)、转谷氨酰胺酶 2 (TG2) 和过氧化物酶 (PXDN) 等酶催化通过广泛的胶原交联促进纤维化进展。近年来的研究已经开始阐明胶原交联通过越来越僵硬和不顺从的 ECM 在独立于炎症的器官纤维化进程中的重要作用。因此，胶原交联和交联酶已成为抗纤维化治疗的新靶点以及新生物标志物的靶点，以正确评估纤维化 ECM 的分辨率。

涵盖的领域：催化胶原蛋白交联的酶的酶促作用及其在器官纤维化中的相关性。基于 2020 年 11 月完成的 Pubmed 搜索以及作者的知识，讨论了专门量化胶原蛋白交联的蛋白水解片段的潜在生物标志物。

专家意见：目前评估纤维化的方法涉及使用侵入性和/或繁琐且昂贵的方法，例如组织活检。因此，对交联胶原蛋白水解片段的微创生物标志物的开发和验证存在未满足的需求。这些生物标志物可能有助于未来几年纤维化消退的发展和正确评估。