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器官纤维化发展中的上皮-间质转化:当前认识与治疗策略

Epithelial-mesenchymal transition in organ fibrosis development: current understanding and treatment strategies.

作者信息

Liu Lexin, Sun Qizhe, Davis Frank, Mao Jianhua, Zhao Hailin, Ma Daqing

机构信息

Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH, UK.

Department of Nephrology and Urology, Pediatric Urolith Center, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, 310003, China.

出版信息

Burns Trauma. 2022 Apr 8;10:tkac011. doi: 10.1093/burnst/tkac011. eCollection 2022.

Abstract

Organ fibrosis is a process in which cellular homeostasis is disrupted and extracellular matrix is excessively deposited. Fibrosis can lead to vital organ failure and there are no effective treatments yet. Although epithelial-mesenchymal transition (EMT) may be one of the key cellular mechanisms, the underlying mechanisms of fibrosis remain largely unknown. EMT is a cell phenotypic process in which epithelial cells lose their cell-to-cell adhesion and polarization, after which they acquire mesenchymal features such as infiltration and migration ability. Upon injurious stimulation in different organs, EMT can be triggered by multiple signaling pathways and is also regulated by epigenetic mechanisms. This narrative review summarizes the current understanding of the underlying mechanisms of EMT in fibrogenesis and discusses potential strategies for attenuating EMT to prevent and/or inhibit fibrosis. Despite better understanding the role of EMT in fibrosis development, targeting EMT and beyond in developing therapeutics to tackle fibrosis is challenging but likely feasible.

摘要

器官纤维化是一个细胞内稳态被破坏且细胞外基质过度沉积的过程。纤维化可导致重要器官衰竭,目前尚无有效治疗方法。尽管上皮-间质转化(EMT)可能是关键的细胞机制之一,但纤维化的潜在机制在很大程度上仍不清楚。EMT是一种细胞表型过程,其中上皮细胞失去细胞间黏附及极性,之后获得诸如浸润和迁移能力等间质特征。在不同器官受到损伤刺激时,EMT可由多种信号通路触发,并且也受表观遗传机制调控。这篇叙述性综述总结了目前对EMT在纤维化发生中潜在机制的理解,并讨论了减弱EMT以预防和/或抑制纤维化的潜在策略。尽管对EMT在纤维化发展中的作用有了更好的理解,但在开发治疗纤维化的疗法中靶向EMT及其他方面具有挑战性,但可能是可行的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab39/8990740/46370758d1ea/tkac011f1.jpg

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