Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients
Por:
Martinez-Castillo, Moises, Hernandez-Barragan, Abigail, Flores-Vasconcelos, Ivonne, Galicia-Moreno, Marina, Rosique-Oramas, Dorothy, Perez-Hernandez, Jose Luis, de la Tijera, Fatima, Montalvo-Jave, Eduardo E., Torre-Delgadillo, Aldo, Cordero-Perez, Paula, Munoz-Espinosa, Linda, KERSHENOBICH, DAVID, Gutierrez-Reyes, Gabriela
Publicada:
27 feb 2021
Categoría:
Hepatology
Resumen:
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(R) and/or
FibroScan(R). 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.
Filiaciones:
Martinez-Castillo, Moises:
Univ Nacl Autonoma Mexico, Gen Hosp Mexico, Liver Pancreas & Motil Lab, Unit Expt Med,Sch Med, Dr Balmis 148 Col Doctores Cuauhtemoc, Mexico City 06726, DF, Mexico
Hernandez-Barragan, Abigail:
Univ Nacl Autonoma Mexico, Gen Hosp Mexico, Liver Pancreas & Motil Lab, Unit Expt Med,Sch Med, Dr Balmis 148 Col Doctores Cuauhtemoc, Mexico City 06726, DF, Mexico
Flores-Vasconcelos, Ivonne:
Univ Nacl Autonoma Mexico, Gen Hosp Mexico, Liver Pancreas & Motil Lab, Unit Expt Med,Sch Med, Dr Balmis 148 Col Doctores Cuauhtemoc, Mexico City 06726, DF, Mexico
Galicia-Moreno, Marina:
Univ Guadalajara, Hlth Sci Univ Ctr, Inst Mol Biol Med & Gene Therapy, Dept Mol Biol & Genom, Guadalajara 06726, Mexico
Rosique-Oramas, Dorothy:
Univ Nacl Autonoma Mexico, Gen Hosp Mexico, Liver Pancreas & Motil Lab, Unit Expt Med,Sch Med, Dr Balmis 148 Col Doctores Cuauhtemoc, Mexico City 06726, DF, Mexico
Perez-Hernandez, Jose Luis:
Gen Hosp Mexico Dr Eduardo Liceaga, Dept Gastroenterol, Mexico City 06726, DF, Mexico
de la Tijera, Fatima:
Gen Hosp Mexico Dr Eduardo Liceaga, Dept Gastroenterol, Mexico City 06726, DF, Mexico
Montalvo-Jave, Eduardo E.:
Univ Nacl Autonoma Mexico, Sch Med, Gen Hosp Mexico Dr Eduardo Liceaga, Dept Gen Surg, Mexico City 06726, DF, Mexico
Torre-Delgadillo, Aldo:
Natl Inst Med Sci & Nutr Salvador Zubiran, Hepatol & Liver Transplant, Mexico City 06726, DF, Mexico
Cordero-Perez, Paula:
Autonomous Univ Nuevo Leon, Univ Hosp Dr Jose Eleuterio Gonzalez, Monterrey 06726, Mexico
Munoz-Espinosa, Linda:
Autonomous Univ Nuevo Leon, Univ Hosp Dr Jose Eleuterio Gonzalez, Monterrey 06726, Mexico
KERSHENOBICH, DAVID:
Natl Inst Med Sci & Nutr Salvador Zubiran, Hepatol & Liver Transplant, Mexico City 06726, DF, Mexico
Gutierrez-Reyes, Gabriela:
Univ Nacl Autonoma Mexico, Gen Hosp Mexico, Liver Pancreas & Motil Lab, Unit Expt Med,Sch Med, Dr Balmis 148 Col Doctores Cuauhtemoc, Mexico City 06726, DF, Mexico
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