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Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice

BACKGROUND: Chondroitin/dermatan sulfate (CS/DS) rich in N-acetylgalactosamine 4,6-bissulfate (GalNAc(4,6SO(4))) residues is present as decorin and/or biglycan in mouse liver, and GalNAc(4,6SO(4)) residues disappeared completely in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST)...

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Autores principales: Habuchi, Hiroko, Ushida, Takahiro, Habuchi, Osami
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983273/
https://www.ncbi.nlm.nih.gov/pubmed/27547834
http://dx.doi.org/10.1016/j.heliyon.2016.e00138
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author Habuchi, Hiroko
Ushida, Takahiro
Habuchi, Osami
author_facet Habuchi, Hiroko
Ushida, Takahiro
Habuchi, Osami
author_sort Habuchi, Hiroko
collection PubMed
description BACKGROUND: Chondroitin/dermatan sulfate (CS/DS) rich in N-acetylgalactosamine 4,6-bissulfate (GalNAc(4,6SO(4))) residues is present as decorin and/or biglycan in mouse liver, and GalNAc(4,6SO(4)) residues disappeared completely in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) knockout (KO) mice. The aim of this study was to investigate whether CS/DS rich in GalNAc(4,6SO(4)) residues participate in the progression or resolution of liver fibrosis. METHODS: Wild type (WT) and GalNAc4S-6ST KO mice were treated with CCl(4) for 5 weeks. After discontinuation of CCl(4) administration, histochemical and biochemical changes and expression of genes related to matrix components were compared between WT and GalNAc4S-6ST KO mice. RESULTS AND CONCLUSION: On 2 days after cessation of CCl(4) administration, higher fibrosis was observed in KO mice than in WT mice by Sirius Red staining. Serum alanine aminotransferase activity was higher in KO mice than in WT mice. Hydroxyproline contents and Sirius Red staining showed that repair of liver fibrosis in the recovery stages appeared to be delayed in KO mice. Expression of mRNA of matrix metalloproteinase (MMP)-2, MMP-13 and versican peaked at 2 days after cessation of CCl(4) administration and was higher in KO mice than in WT mice. Expression of MMP-9 in the recovery stage was lower in KO mice than in WT mice. Our findings demonstrate that defect in GalNAc4S-6ST, which resulted in disappearance of CS/DS containing GalNAc(4,6SO(4)), appear to contribute to progression of liver fibrosis, delayed recovery from fibrosis, and various changes in the expression of proteoglycans and MMPs in carbon tetrachloride–treated mice.
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spelling pubmed-49832732016-08-19 Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice Habuchi, Hiroko Ushida, Takahiro Habuchi, Osami Heliyon Article BACKGROUND: Chondroitin/dermatan sulfate (CS/DS) rich in N-acetylgalactosamine 4,6-bissulfate (GalNAc(4,6SO(4))) residues is present as decorin and/or biglycan in mouse liver, and GalNAc(4,6SO(4)) residues disappeared completely in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) knockout (KO) mice. The aim of this study was to investigate whether CS/DS rich in GalNAc(4,6SO(4)) residues participate in the progression or resolution of liver fibrosis. METHODS: Wild type (WT) and GalNAc4S-6ST KO mice were treated with CCl(4) for 5 weeks. After discontinuation of CCl(4) administration, histochemical and biochemical changes and expression of genes related to matrix components were compared between WT and GalNAc4S-6ST KO mice. RESULTS AND CONCLUSION: On 2 days after cessation of CCl(4) administration, higher fibrosis was observed in KO mice than in WT mice by Sirius Red staining. Serum alanine aminotransferase activity was higher in KO mice than in WT mice. Hydroxyproline contents and Sirius Red staining showed that repair of liver fibrosis in the recovery stages appeared to be delayed in KO mice. Expression of mRNA of matrix metalloproteinase (MMP)-2, MMP-13 and versican peaked at 2 days after cessation of CCl(4) administration and was higher in KO mice than in WT mice. Expression of MMP-9 in the recovery stage was lower in KO mice than in WT mice. Our findings demonstrate that defect in GalNAc4S-6ST, which resulted in disappearance of CS/DS containing GalNAc(4,6SO(4)), appear to contribute to progression of liver fibrosis, delayed recovery from fibrosis, and various changes in the expression of proteoglycans and MMPs in carbon tetrachloride–treated mice. Elsevier 2016-08-08 /pmc/articles/PMC4983273/ /pubmed/27547834 http://dx.doi.org/10.1016/j.heliyon.2016.e00138 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Habuchi, Hiroko
Ushida, Takahiro
Habuchi, Osami
Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice
title Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice
title_full Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice
title_fullStr Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice
title_full_unstemmed Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice
title_short Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice
title_sort mice deficient in n-acetylgalactosamine 4-sulfate 6-o-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983273/
https://www.ncbi.nlm.nih.gov/pubmed/27547834
http://dx.doi.org/10.1016/j.heliyon.2016.e00138
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