Nordic Bioscience, Biomarkers & Research A/S, Herlev, Metabolic Liver Research Program, Denmark.
Duke Molecular Physiology Institute and Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Autoimmun Rev. 2021 Jan;20(1):102706. doi: 10.1016/j.autrev.2020.102706. Epub 2020 Nov 12.
Connective tissue (ConT) remodeling is an essential process in tissue regeneration, where a balanced replacement of old tissue by new tissue occurs. This balance is disturbed in chronic diseases, often autoimmune diseases, usually resulting in the buld up of fibrosis and a gradual loss of organ function. During progression of liver, lung, skin, heart, joint, skeletal and kidney diseasesboth ConT formation and degradation are elevated, which is tightly linked to immune cell activation and a loss of specific cell types and extracellular matrix (ECM) structures that are required for normal organ function. Here, we address the balance of key general and organ specific components of the ECM during homeostasis and in disease, with a focus on collagens, which are emerging as both structural and signaling molecules harbouring neoepitopes and autoantigens that are released during ConT remodeling. Specific collagen molecular signatures of ConT remodeling are linked to disease activity and stage, and to prognosis across different organs. These signatures accompany and further drive disease progression, and often become detectable before clinical disease manifestation (illness). Recent advances allow to quantify and define the nature of ConT remodeling via blood-based assays that measure the levels of well-defined collagen fragments, reflecting different facets of ConT formation and degradation, and associated immunological processes. These novel serum assays are becoming important tools of precision medicine, to detect various chronic and autoimmune diseases before their clinical manifestation, and to non-invasively monitor the efficacy of a broad range of pharmacological interventions.
结缔组织（ConT）重塑是组织再生的一个基本过程，在此过程中，通过新组织对旧组织的平衡替代发生。这种平衡在慢性疾病中被打乱，通常是自身免疫性疾病，通常导致纤维化的积累和器官功能的逐渐丧失。在肝脏、肺、皮肤、心脏、关节、骨骼和肾脏疾病的进展过程中，ConT 的形成和降解都升高，这与免疫细胞的激活以及特定细胞类型和细胞外基质（ECM）结构的丧失密切相关，这些结构对于正常的器官功能是必需的。在这里，我们讨论了 ECM 在稳态和疾病中的关键一般和器官特异性成分的平衡，重点是胶原，胶原作为结构和信号分子，既具有新表位，也具有自身抗原，在 ConT 重塑过程中释放。ConT 重塑的特定胶原分子特征与疾病的活动和阶段以及不同器官的预后相关。这些特征伴随着并进一步推动疾病的进展，并且经常在临床疾病表现（疾病）之前变得可检测。最近的进展允许通过基于血液的测定来定量和定义 ConT 重塑的性质，这些测定测量定义明确的胶原片段的水平，反映 ConT 形成和降解的不同方面，以及相关的免疫过程。这些新的血清测定正在成为精准医学的重要工具，用于在临床表现之前检测各种慢性和自身免疫性疾病，并非侵入性地监测广泛的药理学干预的疗效。
