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

被引:63
作者
Liu, Lexin [1 ,2 ]
Sun, Qizhe [1 ]
Davis, Frank [1 ]
Mao, Jianhua [3 ]
Zhao, Hailin [1 ]
Ma, Daqing [1 ]
机构
[1] Imperial Coll London, Div Anaesthet Pain Med & Intens Care, Dept Surg & Canc, Fac Med,Chelsea & Westminster Hosp, London SW10 9NH, England
[2] Zhejiang Univ, Dept Nephrol & Urol, Pediat Urolith Ctr, Childrens Hosp,Sch Med,Natl Clin Res Ctr Child Hl, Hangzhou 310003, Zhejiang, Peoples R China
[3] Zhejiang Univ, Sch Med, Dept Nephrol, Children Hosp, Hangzhou 310003, Zhejiang, Peoples R China
关键词
EMT; Fibrosis; TGF-beta; Smad; HDAC inhibitors; TGF-beta antibody; Organ fibrosis; Senescence; Extracellular matrix; RENAL INTERSTITIAL FIBROSIS; PULMONARY-FIBROSIS; LIVER FIBROSIS; TGF-BETA/SMAD; TUBULOINTERSTITIAL FIBROSIS; DIABETIC-NEPHROPATHY; HK-2; CELLS; PATHWAY; INHIBITION; EMT;
D O I
10.1093/burnst/tkac011
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
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页数:20
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