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Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model

Heparanase is elevated in various pathological conditions, primarily cancer and inflammation. To investigate the significance and involvement of heparanase in liver fibrosis, we compared the susceptibility of wild-type (WT) and heparanase-overexpressing transgenic (Hpa-tg) mice to carbon tetrachlori...

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Autores principales: Cheng, Xiaowen, Jia, Juan, Zhang, Tianji, Zhang, Xiao, Vlodavsky, Israel, Li, Jin-ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265342/
https://www.ncbi.nlm.nih.gov/pubmed/35805119
http://dx.doi.org/10.3390/cells11132035
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author Cheng, Xiaowen
Jia, Juan
Zhang, Tianji
Zhang, Xiao
Vlodavsky, Israel
Li, Jin-ping
author_facet Cheng, Xiaowen
Jia, Juan
Zhang, Tianji
Zhang, Xiao
Vlodavsky, Israel
Li, Jin-ping
author_sort Cheng, Xiaowen
collection PubMed
description Heparanase is elevated in various pathological conditions, primarily cancer and inflammation. To investigate the significance and involvement of heparanase in liver fibrosis, we compared the susceptibility of wild-type (WT) and heparanase-overexpressing transgenic (Hpa-tg) mice to carbon tetrachloride (CCL4)-induced fibrosis. In comparison with WT mice, Hpa-tg mice displayed a severe degree of tissue damage and fibrosis, including higher necrotic tendency and intensified expression of smooth muscle actin. While damage to the WT liver started to recover after the acute phase, damage to the Hpa-tg liver was persistent. Recovery was attributed, in part, to heparanase-stimulated autophagic activity in response to CCL4, leading to increased apoptosis and necrosis. The total number of stellate cells was significantly higher in the Hpa-tg than the WT liver, likely contributing to the increased amounts of lipid droplets and smooth muscle actin. Our results support the notion that heparanase enhances inflammatory responses, and hence may serve as a target for the treatment of liver damage and fibrosis.
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spelling pubmed-92653422022-07-09 Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model Cheng, Xiaowen Jia, Juan Zhang, Tianji Zhang, Xiao Vlodavsky, Israel Li, Jin-ping Cells Article Heparanase is elevated in various pathological conditions, primarily cancer and inflammation. To investigate the significance and involvement of heparanase in liver fibrosis, we compared the susceptibility of wild-type (WT) and heparanase-overexpressing transgenic (Hpa-tg) mice to carbon tetrachloride (CCL4)-induced fibrosis. In comparison with WT mice, Hpa-tg mice displayed a severe degree of tissue damage and fibrosis, including higher necrotic tendency and intensified expression of smooth muscle actin. While damage to the WT liver started to recover after the acute phase, damage to the Hpa-tg liver was persistent. Recovery was attributed, in part, to heparanase-stimulated autophagic activity in response to CCL4, leading to increased apoptosis and necrosis. The total number of stellate cells was significantly higher in the Hpa-tg than the WT liver, likely contributing to the increased amounts of lipid droplets and smooth muscle actin. Our results support the notion that heparanase enhances inflammatory responses, and hence may serve as a target for the treatment of liver damage and fibrosis. MDPI 2022-06-27 /pmc/articles/PMC9265342/ /pubmed/35805119 http://dx.doi.org/10.3390/cells11132035 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheng, Xiaowen
Jia, Juan
Zhang, Tianji
Zhang, Xiao
Vlodavsky, Israel
Li, Jin-ping
Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model
title Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model
title_full Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model
title_fullStr Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model
title_full_unstemmed Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model
title_short Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model
title_sort heparanase expression propagates liver damage in ccl4-induced mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265342/
https://www.ncbi.nlm.nih.gov/pubmed/35805119
http://dx.doi.org/10.3390/cells11132035
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