单位：[1]Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.医技科室北京市临床医学研究所实验中心首都医科大学附属北京友谊医院[2]Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing, China首都医科大学附属北京友谊医院[3]Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China.临床科室国家中心肝病分中心首都医科大学附属北京友谊医院[4]Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA[5]Institute of Translational Immunology and Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany. .
The cross-linking of structural extracellular matrix (ECM) components, especially fibrillar collagens and elastin, is strongly implicated in fibrosis progression and resistance to fibrosis reversal. Lysyl oxidase family members (LOX and LOXL1 [lysyl oxidase-like 1], LOXL2 [lysyl oxidase-like 2], LOXL3 [lysyl oxidase-like 3], and LOXL4 [lysyl oxidase like 4]) are extracellular copper-dependent enzymes that play a key role in ECM cross-linking, but have also other intracellular functions relevant to fibrosis and carcinogenesis. Although the expression of most LOX family members is elevated in experimental liver fibrosis of diverse etiologies, their individual contribution to fibrosis is incompletely understood. Inhibition of the LOX family as a whole and of LOX, LOXL1, and LOXL2 specifically has been shown to suppress fibrosis progression and accelerate its reversal in rodent models of cardiac, renal, pulmonary, and liver fibrosis. Recent disappointing clinical trials with a monoclonal antibody against LOXL2 (simtuzumab) in patients with pulmonary and liver fibrosis dampened enthusiasm for LOX family member inhibition. However, this unexpected negative outcome may be related to the inefficient antibody, rather than to LOXL2, not qualifying as a relevant antifibrotic target. Moreover, LOX family members other than LOXL2 may prove to be attractive therapeutic targets. In this review, we summarize the structural hallmarks, expression patterns, covalent cross-linking activities, and modes of regulation of LOX family members and discuss the clinical potential of their inhibition to treat fibrosis in general and liver fibrosis in particular.
第一作者单位：[1]Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.[2]Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[1]Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.[2]Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing, China[3]Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China.[4]Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA[5]Institute of Translational Immunology and Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany. .[*1]Beijing Friendship Hospital, Capital Medical University, No. 95 Y ong'an road, Xicheng District, Beijing 100050, China[*2]Institute of Translational Immunology and Research, Center for Immunotherapy, University Medical Center,Langenbeckstra Be 1,55131 Mainz， Germany
推荐引用方式(GB/T 7714)：
Chen Wei,Yang Aiting,Jia Jidong,et al.Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis[J].HEPATOLOGY.2020,72(2):729-741.doi:10.1002/hep.31236.
APA：
Chen Wei,Yang Aiting,Jia Jidong,Popov Yury V,Schuppan Detlef&You Hong.(2020).Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis.HEPATOLOGY,72,(2)
MLA：
Chen Wei,et al."Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis".HEPATOLOGY 72..2(2020):729-741
医学