<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Klepfish, M.</style></author><author><style face="normal" font="default" size="100%">Gross, T.</style></author><author><style face="normal" font="default" size="100%">Vugman, M.</style></author><author><style face="normal" font="default" size="100%">Afratis, N. A.</style></author><author><style face="normal" font="default" size="100%">Havusha-Laufer, S.</style></author><author><style face="normal" font="default" size="100%">Brazowski, E.</style></author><author><style face="normal" font="default" size="100%">Solomonov, I.</style></author><author><style face="normal" font="default" size="100%">Varol, C.</style></author><author><style face="normal" font="default" size="100%">Sagi, I.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">LOXL2 Inhibition Paves the Way for Macrophage-Mediated Collagen Degradation in Liver Fibrosis</style></title><secondary-title><style face="normal" font="default" size="100%">Front Immunol </style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">*liver fibrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">*liver macrophages</style></keyword><keyword><style  face="normal" font="default" size="100%">*lysyl oxidase like 2 (LOXL2)</style></keyword><keyword><style  face="normal" font="default" size="100%">*matrix metalloproteinase-14 (MMP-14)</style></keyword><keyword><style  face="normal" font="default" size="100%">*matrix metalloproteinases (MMPs)</style></keyword><keyword><style  face="normal" font="default" size="100%">*monocyte-derived macrophages</style></keyword><keyword><style  face="normal" font="default" size="100%">Amino Acid Oxidoreductases/*antagonists &amp; inhibitors</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Monoclonal/pharmacology</style></keyword><keyword><style  face="normal" font="default" size="100%">Collagen/drug effects/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Extracellular Matrix/drug effects/metabolism/pathology</style></keyword><keyword><style  face="normal" font="default" size="100%">Liver Cirrhosis/*pathology</style></keyword><keyword><style  face="normal" font="default" size="100%">Macrophages/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Matrix Metalloproteinases/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year></dates><edition><style face="normal" font="default" size="100%">20200331</style></edition><volume><style face="normal" font="default" size="100%">11</style></volume><pages><style face="normal" font="default" size="100%">480</style></pages><isbn><style face="normal" font="default" size="100%">1664-3224 (Electronic)1664-3224 (Linking)</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Liver fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) proteins and enzymes, especially fibrillary collagens, and represents a major cause of morbidity and mortality worldwide. Lysyl oxidases (LOXs) drive covalent crosslinking of collagen fibers, thereby promoting stabilization and accumulation of liver fibrosis while limiting its resolution. Here we show in a carbon tetrachloride (CCl4)-induced liver fibrosis murine model that treatment with a novel anti-lysyl oxidase like 2 (LOXL2) neutralizing antibody, which targets extracellular LOXL2, significantly improves fibrosis resolution. LOXL2 inhibition following the onset of fibrosis accelerated and augmented collagen degradation. This was accompanied by increased localization of reparative monocyte-derived macrophages (MoMFs) in the proximity of fibrotic fibers and their representation in the liver. These cells secreted collagenolytic matrix metalloproteinases (MMPs) and, in particular, the membrane-bound MT1-MMP (MMP-14) collagenase. Inducible and selective ablation of infiltrating MoMFs negated the increased &quot;on-fiber&quot; accumulation of MMP-14-expressing MoMFs and the accelerated collagenolytic activity observed in the anti-LOXL2-treated mice. Many studies of liver fibrosis focus on preventing the progression of the fibrotic process. In contrast, the therapeutic mechanism of LOXL2 inhibition presented herein aims at reversing existing fibrosis and facilitating endogenous liver regeneration by paving the way for collagenolytic macrophages.</style></abstract><accession-num><style face="normal" font="default" size="100%">32296422</style></accession-num><notes><style face="normal" font="default" size="100%">Klepfish, MordehayGross, TamarVugman, MilenaAfratis, Nikolaos AHavusha-Laufer, SapirBrazowski, EliSolomonov, InnaVarol, ChenSagi, IritengResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Switzerland2020/04/17Front Immunol. 2020 Mar 31;11:480. doi: 10.3389/fimmu.2020.00480. eCollection 2020.</style></notes><custom2><style face="normal" font="default" size="100%">PMC7136575</style></custom2><auth-address><style face="normal" font="default" size="100%">Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel.Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.</style></auth-address><remote-database-name><style face="normal" font="default" size="100%">Medline</style></remote-database-name><remote-database-provider><style face="normal" font="default" size="100%">NLM</style></remote-database-provider></record></records></xml>