EXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS

Imbalance of the proteolysis/antiproteolysis system is known to be among key components of immunofibrogenesis of liver in cases of chronic hepatitis C. To evaluate these aspects, we studied several factors of liver tissue remodeling in blood serum and local samples from HCV patients associated with...

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Autores principales: I. S. Gorelova, L. F. Sklyar, E. V. Markelova, A. I. Simakova, I. V. Zenin
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Publicado: SPb RAACI 2017
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spelling oai:doaj.org-article:9e515edd2f23400d82078c0fd53507372021-11-18T08:03:45ZEXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS1563-06252313-741X10.15789/1563-0625-2017-1-35-44https://doaj.org/article/9e515edd2f23400d82078c0fd53507372017-01-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1163https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XImbalance of the proteolysis/antiproteolysis system is known to be among key components of immunofibrogenesis of liver in cases of chronic hepatitis C. To evaluate these aspects, we studied several factors of liver tissue remodeling in blood serum and local samples from HCV patients associated with liver fibrosis. We determined the levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), MMP-9/TIMP-1 and MMP-9/TIMP-2 complexes. Clinical, laboratory and instrumental examinations have been made for 81 patients with chronic hepatitis C who did not receive antiviral therapy, and 22 healthy volunteers. Extracellular matrix protein (ECM) profile was studied in 103 serum blood samples and 32 liver supernates using ELISA technique. Statistically significant increase of MMP-9 contents (p < 0.05) and its complexes with TIMP-1 (p < 0.05) and TIMP-2 (p < 0.01), as well as low levels of type 1 inhibitor (p < 0.05) were revealed in blood serum of HCV-infected patients, as compared with control group. Protein assays in liver supernates of hepatitis C patients reflecting extracellular matrix state revealed an eight-fold increase in MMP-9/ TIMP-1 complex, as compared with control group (p < 0.05). The values of other proteolytic/antiproteolytic factors proved to be low (p < 0.05). An imbalance in protease contents in blood serum and liver biopsies was revealed, showing differently directed changes. I.e., serum values of MMP-9, TIMP-1 and MMP-9/TIMP-2 during transition of liver fibrosis to cirrhosis (F0 to F4) became decreased (p < 0.05), associated with increased liver concentrations of these proteolytic enzymes (p < 0.05). In summary, we conclude that the data obtained in our study suggest an imbalance of proteolysis/antiproteolysis system leads to a dysregulated liver tissue remodeling in patients with chronic hepatitis C.I. S. GorelovaL. F. SklyarE. V. MarkelovaA. I. SimakovaI. V. ZeninSPb RAACIarticlematrix metalloproteinasetissue inhibitor of matrix metalloproteinasechronic hepatitis cliver fibrosisImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 19, Iss 1, Pp 35-44 (2017)
institution DOAJ
collection DOAJ
language RU
topic matrix metalloproteinase
tissue inhibitor of matrix metalloproteinase
chronic hepatitis c
liver fibrosis
Immunologic diseases. Allergy
RC581-607
spellingShingle matrix metalloproteinase
tissue inhibitor of matrix metalloproteinase
chronic hepatitis c
liver fibrosis
Immunologic diseases. Allergy
RC581-607
I. S. Gorelova
L. F. Sklyar
E. V. Markelova
A. I. Simakova
I. V. Zenin
EXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS
description Imbalance of the proteolysis/antiproteolysis system is known to be among key components of immunofibrogenesis of liver in cases of chronic hepatitis C. To evaluate these aspects, we studied several factors of liver tissue remodeling in blood serum and local samples from HCV patients associated with liver fibrosis. We determined the levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), MMP-9/TIMP-1 and MMP-9/TIMP-2 complexes. Clinical, laboratory and instrumental examinations have been made for 81 patients with chronic hepatitis C who did not receive antiviral therapy, and 22 healthy volunteers. Extracellular matrix protein (ECM) profile was studied in 103 serum blood samples and 32 liver supernates using ELISA technique. Statistically significant increase of MMP-9 contents (p < 0.05) and its complexes with TIMP-1 (p < 0.05) and TIMP-2 (p < 0.01), as well as low levels of type 1 inhibitor (p < 0.05) were revealed in blood serum of HCV-infected patients, as compared with control group. Protein assays in liver supernates of hepatitis C patients reflecting extracellular matrix state revealed an eight-fold increase in MMP-9/ TIMP-1 complex, as compared with control group (p < 0.05). The values of other proteolytic/antiproteolytic factors proved to be low (p < 0.05). An imbalance in protease contents in blood serum and liver biopsies was revealed, showing differently directed changes. I.e., serum values of MMP-9, TIMP-1 and MMP-9/TIMP-2 during transition of liver fibrosis to cirrhosis (F0 to F4) became decreased (p < 0.05), associated with increased liver concentrations of these proteolytic enzymes (p < 0.05). In summary, we conclude that the data obtained in our study suggest an imbalance of proteolysis/antiproteolysis system leads to a dysregulated liver tissue remodeling in patients with chronic hepatitis C.
format article
author I. S. Gorelova
L. F. Sklyar
E. V. Markelova
A. I. Simakova
I. V. Zenin
author_facet I. S. Gorelova
L. F. Sklyar
E. V. Markelova
A. I. Simakova
I. V. Zenin
author_sort I. S. Gorelova
title EXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS
title_short EXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS
title_full EXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS
title_fullStr EXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS
title_full_unstemmed EXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS
title_sort extracellular matrix condition in case of hcvassociated liver fibrosis
publisher SPb RAACI
publishDate 2017
url https://doaj.org/article/9e515edd2f23400d82078c0fd5350737
work_keys_str_mv AT isgorelova extracellularmatrixconditionincaseofhcvassociatedliverfibrosis
AT lfsklyar extracellularmatrixconditionincaseofhcvassociatedliverfibrosis
AT evmarkelova extracellularmatrixconditionincaseofhcvassociatedliverfibrosis
AT aisimakova extracellularmatrixconditionincaseofhcvassociatedliverfibrosis
AT ivzenin extracellularmatrixconditionincaseofhcvassociatedliverfibrosis
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