Suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis?
Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novel in vitro evidence that the histone deacetylases inhibitor suberoylanilide hydroxamic ac...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
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European Respiratory Society
2009
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/34604 |
| _version_ | 1848754268037709824 |
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| author | Wang, Z. Chen, C. Finger, S. Kwajah, M. Jung, M. Schwarz, H. Swanson, N. Lareu, Ricardo Raghunath, M. |
| author_facet | Wang, Z. Chen, C. Finger, S. Kwajah, M. Jung, M. Schwarz, H. Swanson, N. Lareu, Ricardo Raghunath, M. |
| author_sort | Wang, Z. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novel in vitro evidence that the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA), an FDA approved anti-cancer drug, has antifibrotic and anti-inflammatory potential. Human lung fibroblasts (fetal, adult and idiopathic adult pulmonary fibrosis) were treated with transforming growth factor (TGF)-β1 with or without SAHA. Collagen deposition, α-smooth muscle actin (α-SMA) expression, matrix metalloproteinase (MMP)1 activity, tissue inhibitor of MMP (TIMP)1 production, apoptosis and cell proliferation were assessed. Pro-inflammatory cytokines relevant to pulmonary fibrosis were assayed in SAHA-treated human peripheral blood mononuclear cells (PBMC) and its subpopulations.SAHA abrogated TGF-β1 effects on all the fibroblast lines by preventing their transdifferentiation into α-SMA positive myofibroblasts and increased collagen deposition without inducing apoptosis. However, MMP1 activity and TIMP1 production was modulated without a clear fibrolytic effect. SAHA also inhibited serum-induced proliferation of the fibroblast lines and caused hyperacetylation of α-tubulin and histone. Cytokine secretion was inhibited from PBMC and lymphocytes at nonapoptotic concentrations. Taken together, these data demonstrate combined antifibrotic and anti-inflammatory properties of SAHA, suggesting its therapeutic potential for pulmonary fibrosis. |
| first_indexed | 2025-11-14T08:37:42Z |
| format | Journal Article |
| id | curtin-20.500.11937-34604 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:37:42Z |
| publishDate | 2009 |
| publisher | European Respiratory Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-346042017-09-13T15:13:58Z Suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis? Wang, Z. Chen, C. Finger, S. Kwajah, M. Jung, M. Schwarz, H. Swanson, N. Lareu, Ricardo Raghunath, M. suberoylanilide hydroxamic acid pulmonary fibrosis collagen Antifibrotic histone deacetylase inhibitor fibroblast Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novel in vitro evidence that the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA), an FDA approved anti-cancer drug, has antifibrotic and anti-inflammatory potential. Human lung fibroblasts (fetal, adult and idiopathic adult pulmonary fibrosis) were treated with transforming growth factor (TGF)-β1 with or without SAHA. Collagen deposition, α-smooth muscle actin (α-SMA) expression, matrix metalloproteinase (MMP)1 activity, tissue inhibitor of MMP (TIMP)1 production, apoptosis and cell proliferation were assessed. Pro-inflammatory cytokines relevant to pulmonary fibrosis were assayed in SAHA-treated human peripheral blood mononuclear cells (PBMC) and its subpopulations.SAHA abrogated TGF-β1 effects on all the fibroblast lines by preventing their transdifferentiation into α-SMA positive myofibroblasts and increased collagen deposition without inducing apoptosis. However, MMP1 activity and TIMP1 production was modulated without a clear fibrolytic effect. SAHA also inhibited serum-induced proliferation of the fibroblast lines and caused hyperacetylation of α-tubulin and histone. Cytokine secretion was inhibited from PBMC and lymphocytes at nonapoptotic concentrations. Taken together, these data demonstrate combined antifibrotic and anti-inflammatory properties of SAHA, suggesting its therapeutic potential for pulmonary fibrosis. 2009 Journal Article http://hdl.handle.net/20.500.11937/34604 10.1183/09031936.00084808 European Respiratory Society unknown |
| spellingShingle | suberoylanilide hydroxamic acid pulmonary fibrosis collagen Antifibrotic histone deacetylase inhibitor fibroblast Wang, Z. Chen, C. Finger, S. Kwajah, M. Jung, M. Schwarz, H. Swanson, N. Lareu, Ricardo Raghunath, M. Suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis? |
| title | Suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis? |
| title_full | Suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis? |
| title_fullStr | Suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis? |
| title_full_unstemmed | Suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis? |
| title_short | Suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis? |
| title_sort | suberoylanilide hydroxamic acid – a potential epigenetic therapeutic agent for lung fibrosis? |
| topic | suberoylanilide hydroxamic acid pulmonary fibrosis collagen Antifibrotic histone deacetylase inhibitor fibroblast |
| url | http://hdl.handle.net/20.500.11937/34604 |