Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients  

作　　者：Moises Martinez-Castillo Abigail Hernandez-Barragan Ivonne Flores-Vasconcelos Marina Galicia-Moreno Dorothy Rosique-Oramas Jose Luis Perez-Hernandez Fatima Higuera-De la Tijera Eduardo E Montalvo-Jave Aldo Torre-Delgadillo Paula Cordero-Perez Linda Muñoz-Espinosa David Kershenobich Gabriela Gutierrez-Reyes 

机构地区：[1]Liver,Pancreas and Motility Laboratory,Unit of Experimental Medicine,School of Medicine,General Hospital of Mexico,Universidad Nacional Autonoma de Mexico,Mexico City 06726,Mexico [2]Department of Molecular Biology and Genomics,Institute of Molecular Biology in Medicine and Gene Therapy,Health Science University Center,University of Guadalajara,Guadalajara 06726,Mexico [3]Department of Gastroenterology,General Hospital of Mexico“Dr.Eduardo Liceaga,”Mexico City 06726,Mexico [4]Department of General Surgery,General Hospital of Mexico“Dr.Eduardo Liceaga,”School of Medicine,Universidad Nacional Autonoma de Mexico,Mexico City 06726,Mexico [5]Hepatology and Liver Transplant,National Institute of Medical Sciences and Nutrition“Salvador Zubirán,”Mexico City 06726,Mexico [6]University Hospital“Dr.JoséEleuterio González,”Autonomous University of Nuevo Leon,Monterrey 06726,Mexico

出　　处：《World Journal of Hepatology》2021年第2期218-232,共15页世界肝病学杂志（英文版）（电子版）

基　　金：the National Council for Science and Technology,No.SALUD-2016-272579 and No.PAPIIT-UNAM TA200515.

摘　　要：BACKGROUND Matrix metalloproteinases(MMPs)participate in the degradation of extracellular matrix compounds,maintaining the homeostasis between fibrogenesis and fibrolytic processes in the liver.However,there are few studies on the regulation of liver MMPs in fibrosis progression in humans.AIM To assess the production activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C(CHC).METHODS A prospective,cross-sectional,multicenter study was conducted.CHC patients were categorized in fibrosis grades through FibroTest®and/or FibroScan®.Serum MMP-2,-7,and-9 were determined by western blot and multiplex suspension array assays.Differences were validated by the Kruskal-Wallis and Mann-Whitney U tests.The Spearman correlation coefficient and area under the receiver operating characteristic curve were calculated.Collagenolytic and gelatinase activity was determined through the Azocoll substrate and zymogram test,whereas tissue inhibitor of metalloproteinase-1 production was determined by dot blot assays.RESULTS Serum concentrations of the MMPs evaluated were higher in CHC patients than in healthy subjects.MMP-7 distinguished early and advanced stages,with a correlation of 0.32(P<0.001),and the area under the receiver operating characteristic displayed moderate sensitivity and specificity for MMP-7 in F4(area under the receiver operating characteristic,0.705;95%confidence interval:0.605-0.805;P<0.001).Collagenolytic activity was detected at F0 and F1,whereas gelatinase activity was not detected at any fibrosis stage.Tissue inhibitor of metalloproteinase-1 determination showed upregulation in F0 and F1 but downregulation in F2(P<0.001).CONCLUSION High concentrations of inactive MMPs were present in the serum of CHC patients,reflecting the impossibility to restrain liver fibrosis progression.MMPs could be good diagnostic candidates and therapeutic targets for improving novel strategies to reverse liver fibrosis in CHC.

关 键 词：Extracellular matrix Matrix metalloproteinases Liver fibrosis Chronic hepatitis C FIBROGENESIS Fibrolysis 

分 类 号：R512.63[医药卫生—内科学] R575.2[医药卫生—临床医学]