Cargando…
Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma
The tight-skin (TSK/+) mouse, a genetic model of systemic sclerosis (SSc), develops cutaneous fibrosis and defects in pulmonary architecture. Because hepatocyte growth factor (HGF) is an important mitogen and morphogen that contributes to the repair process after tissue injury, we investigated the r...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2006
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794503/ https://www.ncbi.nlm.nih.gov/pubmed/17049072 http://dx.doi.org/10.1186/ar2068 |
_version_ | 1782132194511159296 |
---|---|
author | Iwasaki, Tsuyoshi Imado, Takehito Kitano, Sachie Sano, Hajime |
author_facet | Iwasaki, Tsuyoshi Imado, Takehito Kitano, Sachie Sano, Hajime |
author_sort | Iwasaki, Tsuyoshi |
collection | PubMed |
description | The tight-skin (TSK/+) mouse, a genetic model of systemic sclerosis (SSc), develops cutaneous fibrosis and defects in pulmonary architecture. Because hepatocyte growth factor (HGF) is an important mitogen and morphogen that contributes to the repair process after tissue injury, we investigated the role of HGF in cutaneous fibrosis and pulmonary architecture defects in SSc using TSK/+ mice. TSK/+ mice were injected in the gluteal muscle with either hemagglutinating virus of Japan (HVJ) liposomes containing 8 μg of a human HGF expression vector (HGF-HVJ liposomes) or a mock vector (untreated control). Gene transfer was repeated once weekly for 8 weeks. The effects of HGF gene transfection on the histopathology and expression of tumor growth factor (TGF)-β and IL-4 mRNA in TSK/+ mice were examined. The effect of recombinant HGF on IL-4 production by TSK/+ CD4(+ )T cells stimulated by allogeneic dendritic cells (DCs) in vitro was also examined. Histologic analysis revealed that HGF gene transfection in TSK/+ mice resulted in a marked reduction of hypodermal thickness, including the subcutaneous connective tissue layer. The hypodermal thickness of HGF-treated TSK/+ mice was decreased two-fold to three-fold compared with untreated TSK/+ mice. However, TSK/+ associated defects in pulmonary architecture were unaffected by HGF gene transfection. HGF gene transfection significantly inhibited the expression of IL-4 and TGF-β1 mRNA in the spleen and skin but not in the lung. We also performed a mixed lymphocyte culture and examined the effect of recombinant HGF on the generation of IL-4. Recombinant HGF significantly inhibited IL-4 production in TSK/+ CD4(+ )T cells stimulated by allogeneic DCs. HGF gene transfection inhibited IL-4 and TGF-β mRNA expression, which has been postulated to have a major role in fibrinogenesis and reduced hypodermal thickness, including the subcutaneous connective tissue layer of TSK/+ mice. HGF might represent a novel strategy for the treatment of SSc. |
format | Text |
id | pubmed-1794503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-17945032007-02-08 Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma Iwasaki, Tsuyoshi Imado, Takehito Kitano, Sachie Sano, Hajime Arthritis Res Ther Research Article The tight-skin (TSK/+) mouse, a genetic model of systemic sclerosis (SSc), develops cutaneous fibrosis and defects in pulmonary architecture. Because hepatocyte growth factor (HGF) is an important mitogen and morphogen that contributes to the repair process after tissue injury, we investigated the role of HGF in cutaneous fibrosis and pulmonary architecture defects in SSc using TSK/+ mice. TSK/+ mice were injected in the gluteal muscle with either hemagglutinating virus of Japan (HVJ) liposomes containing 8 μg of a human HGF expression vector (HGF-HVJ liposomes) or a mock vector (untreated control). Gene transfer was repeated once weekly for 8 weeks. The effects of HGF gene transfection on the histopathology and expression of tumor growth factor (TGF)-β and IL-4 mRNA in TSK/+ mice were examined. The effect of recombinant HGF on IL-4 production by TSK/+ CD4(+ )T cells stimulated by allogeneic dendritic cells (DCs) in vitro was also examined. Histologic analysis revealed that HGF gene transfection in TSK/+ mice resulted in a marked reduction of hypodermal thickness, including the subcutaneous connective tissue layer. The hypodermal thickness of HGF-treated TSK/+ mice was decreased two-fold to three-fold compared with untreated TSK/+ mice. However, TSK/+ associated defects in pulmonary architecture were unaffected by HGF gene transfection. HGF gene transfection significantly inhibited the expression of IL-4 and TGF-β1 mRNA in the spleen and skin but not in the lung. We also performed a mixed lymphocyte culture and examined the effect of recombinant HGF on the generation of IL-4. Recombinant HGF significantly inhibited IL-4 production in TSK/+ CD4(+ )T cells stimulated by allogeneic DCs. HGF gene transfection inhibited IL-4 and TGF-β mRNA expression, which has been postulated to have a major role in fibrinogenesis and reduced hypodermal thickness, including the subcutaneous connective tissue layer of TSK/+ mice. HGF might represent a novel strategy for the treatment of SSc. BioMed Central 2006 2006-10-18 /pmc/articles/PMC1794503/ /pubmed/17049072 http://dx.doi.org/10.1186/ar2068 Text en Copyright © 2006 Iwasaki et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Iwasaki, Tsuyoshi Imado, Takehito Kitano, Sachie Sano, Hajime Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma |
title | Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma |
title_full | Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma |
title_fullStr | Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma |
title_full_unstemmed | Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma |
title_short | Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma |
title_sort | hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794503/ https://www.ncbi.nlm.nih.gov/pubmed/17049072 http://dx.doi.org/10.1186/ar2068 |
work_keys_str_mv | AT iwasakitsuyoshi hepatocytegrowthfactoramelioratesdermalsclerosisinthetightskinmousemodelofscleroderma AT imadotakehito hepatocytegrowthfactoramelioratesdermalsclerosisinthetightskinmousemodelofscleroderma AT kitanosachie hepatocytegrowthfactoramelioratesdermalsclerosisinthetightskinmousemodelofscleroderma AT sanohajime hepatocytegrowthfactoramelioratesdermalsclerosisinthetightskinmousemodelofscleroderma |