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纤维化:从机制到药物

Fibrosis: from mechanisms to medicines.

作者信息

Henderson Neil C, Rieder Florian, Wynn Thomas A

机构信息

University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK.

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

出版信息

Nature. 2020 Nov;587(7835):555-566. doi: 10.1038/s41586-020-2938-9. Epub 2020 Nov 25.

Abstract

Fibrosis can affect any organ and is responsible for up to 45% of all deaths in the industrialized world. It has long been thought to be relentlessly progressive and irreversible, but both preclinical models and clinical trials in various organ systems have shown that fibrosis is a highly dynamic process. This has clear implications for therapeutic interventions that are designed to capitalize on this inherent plasticity. However, despite substantial progress in our understanding of the pathobiology of fibrosis, a translational gap remains between the identification of putative antifibrotic targets and conversion of this knowledge into effective treatments in humans. Here we discuss the transformative experimental strategies that are being leveraged to dissect the key cellular and molecular mechanisms that regulate fibrosis, and the translational approaches that are enabling the emergence of precision medicine-based therapies for patients with fibrosis.

摘要

纤维化可累及任何器官,在工业化国家,其导致的死亡占总死亡人数的比例高达45%。长期以来,人们一直认为纤维化是持续进展且不可逆转的,但各种器官系统的临床前模型和临床试验均表明,纤维化是一个高度动态的过程。这对于旨在利用这种内在可塑性的治疗干预措施具有明确的意义。然而,尽管我们在纤维化病理生物学的理解方面取得了重大进展,但在确定假定的抗纤维化靶点与将这些知识转化为人类有效治疗方法之间仍存在转化差距。在此,我们讨论了用于剖析调节纤维化的关键细胞和分子机制的变革性实验策略,以及促成基于精准医学的纤维化患者治疗方法出现的转化方法。

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