Fibrosis: from mechanisms to medicines

被引:1224
作者
Henderson, Neil C. [1 ,2 ]
Rieder, Florian [3 ,4 ]
Wynn, Thomas A. [5 ]
机构
[1] Univ Edinburgh, Ctr Inflammat Res, Queens Med Res Inst, Edinburgh BioQuarter, Edinburgh, Midlothian, Scotland
[2] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland
[3] Cleveland Clin Fdn, Lerner Res Inst, Dept Inflammat & Immun, 9500 Euclid Ave, Cleveland, OH 44195 USA
[4] Cleveland Clin Fdn, Dept Gastroenterol Hepatol & Nutr, Digest Dis & Surg Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA
[5] Pfizer Worldwide Res Dev & Med, Inflammat & Immunol Res Unit, Cambridge, MA 02140 USA
基金
英国医学研究理事会; 英国惠康基金; 美国国家卫生研究院;
关键词
IDIOPATHIC PULMONARY-FIBROSIS; HEPATIC STELLATE CELLS; GROWTH-FACTOR-BETA; ACTIVATES LATENT TGF-BETA-1; TGF-BETA; LIVER FIBROSIS; MYOFIBROBLAST DIFFERENTIATION; MATRIX METALLOPROTEINASES; CAVITY MACROPHAGES; DUCTULAR REACTION;
D O I
10.1038/s41586-020-2938-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:555 / 566
页数:12
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