Cargando…
Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a cytoprotective agent in several organ systems but its roles in liver fibrosis are unclear. We studied the roles of HB-EGF in experimental liver fibrosis in mice and during hepatic stellate cell (HSC) activation. Thioacetamide (...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338873/ https://www.ncbi.nlm.nih.gov/pubmed/22330337 http://dx.doi.org/10.1038/labinvest.2012.3 |
_version_ | 1782231279993880576 |
---|---|
author | Huang, Guangcun Besner, Gail E. Brigstock, David R. |
author_facet | Huang, Guangcun Besner, Gail E. Brigstock, David R. |
author_sort | Huang, Guangcun |
collection | PubMed |
description | Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a cytoprotective agent in several organ systems but its roles in liver fibrosis are unclear. We studied the roles of HB-EGF in experimental liver fibrosis in mice and during hepatic stellate cell (HSC) activation. Thioacetamide (TAA; 100mg/kg) was administered by intra-peritoneal injection three times a week for 4 weeks to wild-type HB-EGF(+/+) or HB-EGF-null (HB-EGF(−/−)) male mice. Livers were examined for histology and expression of key fibrotic markers. Primary cultured HSC isolated from untreated HB-EGF(+/+) or HB-EGF(−/−) mice were examined for fibrotic markers and/or cell migration either during culture-induced activation or after exogenous HB-EGF (100 ng/ml) treatment. TAA induced liver fibrosis in both HB-EGF(+/+) and HB-EGF(−/−) mice. Hepatic HB-EGF expression was decreased in TAA-treated HB-EGF(+/+) mice by 37.6% (p < 0.05) as compared to animals receiving saline alone. HB-EGF(−/−) mice treated with TAA showed increased hepatic α-smooth muscle actin-positive cells and collagen deposition, and, as compared to HB-EGF(+/+) mice, TAA-stimulated hepatic mRNA levels in HB-EGF(−/−) mice were, respectively, 2.1-, 1.7-, 1.8-, 2.2-, 1.2-, or 3.3-fold greater for α-smooth muscle actin, α1 chain of collagen I or III (COL1A1 or COL3A1), transforming growth factor-β1, connective tissue growth factor, or tissue inhibitor of metalloproteinase-1 (p < 0.05). HB-EGF expression was detectable in primary cultured HSC from HB-EGF(+/+) mice. Both endogenous and exogenous HB-EGF inhibited HSC activation in primary culture, and HB-EGF enhanced HSC migration. These findings suggest that HB-EGF gene knockout in mice increases susceptibility to chronic TAA-induced hepatic fibrosis and that HB-EGF expression or action is associated with suppression of fibrogenic pathways in HSC. |
format | Online Article Text |
id | pubmed-3338873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-33388732012-11-01 Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice Huang, Guangcun Besner, Gail E. Brigstock, David R. Lab Invest Article Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a cytoprotective agent in several organ systems but its roles in liver fibrosis are unclear. We studied the roles of HB-EGF in experimental liver fibrosis in mice and during hepatic stellate cell (HSC) activation. Thioacetamide (TAA; 100mg/kg) was administered by intra-peritoneal injection three times a week for 4 weeks to wild-type HB-EGF(+/+) or HB-EGF-null (HB-EGF(−/−)) male mice. Livers were examined for histology and expression of key fibrotic markers. Primary cultured HSC isolated from untreated HB-EGF(+/+) or HB-EGF(−/−) mice were examined for fibrotic markers and/or cell migration either during culture-induced activation or after exogenous HB-EGF (100 ng/ml) treatment. TAA induced liver fibrosis in both HB-EGF(+/+) and HB-EGF(−/−) mice. Hepatic HB-EGF expression was decreased in TAA-treated HB-EGF(+/+) mice by 37.6% (p < 0.05) as compared to animals receiving saline alone. HB-EGF(−/−) mice treated with TAA showed increased hepatic α-smooth muscle actin-positive cells and collagen deposition, and, as compared to HB-EGF(+/+) mice, TAA-stimulated hepatic mRNA levels in HB-EGF(−/−) mice were, respectively, 2.1-, 1.7-, 1.8-, 2.2-, 1.2-, or 3.3-fold greater for α-smooth muscle actin, α1 chain of collagen I or III (COL1A1 or COL3A1), transforming growth factor-β1, connective tissue growth factor, or tissue inhibitor of metalloproteinase-1 (p < 0.05). HB-EGF expression was detectable in primary cultured HSC from HB-EGF(+/+) mice. Both endogenous and exogenous HB-EGF inhibited HSC activation in primary culture, and HB-EGF enhanced HSC migration. These findings suggest that HB-EGF gene knockout in mice increases susceptibility to chronic TAA-induced hepatic fibrosis and that HB-EGF expression or action is associated with suppression of fibrogenic pathways in HSC. 2012-02-13 2012-05 /pmc/articles/PMC3338873/ /pubmed/22330337 http://dx.doi.org/10.1038/labinvest.2012.3 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Huang, Guangcun Besner, Gail E. Brigstock, David R. Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice |
title | Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice |
title_full | Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice |
title_fullStr | Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice |
title_full_unstemmed | Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice |
title_short | Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice |
title_sort | heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338873/ https://www.ncbi.nlm.nih.gov/pubmed/22330337 http://dx.doi.org/10.1038/labinvest.2012.3 |
work_keys_str_mv | AT huangguangcun heparinbindingepidermalgrowthfactorlikegrowthfactorsuppressesexperimentalliverfibrosisinmice AT besnergaile heparinbindingepidermalgrowthfactorlikegrowthfactorsuppressesexperimentalliverfibrosisinmice AT brigstockdavidr heparinbindingepidermalgrowthfactorlikegrowthfactorsuppressesexperimentalliverfibrosisinmice |