Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models
Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Despite several studies on SSc treatments, effective treatments for SSc are still lacking. Since evidence suggests an association between intestinal microbiota and SSc, we focused on butyrat...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| author | Hee Jin Park Ok-Yi Jeong Sung Hak Chun Yun Hong Cheon Mingyo Kim Suhee Kim Sang-Il Lee |
| author_facet | Hee Jin Park Ok-Yi Jeong Sung Hak Chun Yun Hong Cheon Mingyo Kim Suhee Kim Sang-Il Lee |
| author_sort | Hee Jin Park |
| collection | DOAJ |
| description | Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Despite several studies on SSc treatments, effective treatments for SSc are still lacking. Since evidence suggests an association between intestinal microbiota and SSc, we focused on butyrate, which has beneficial effects in autoimmune diseases as a bacterial metabolite. Here, we investigated the therapeutic potential of sodium butyrate (SB) using a bleomycin-induced fibrosis mouse model of SSc and human dermal fibroblasts (HDFs). SB attenuated bleomycin-induced dermal and lung fibrosis in mice. SB influenced fecal microbiota composition (phyla Actinobacteria and Bacteroidetes, genera <i>Bifidobacterium</i> and <i>Ruminococcus_g2</i>). SB controlled macrophage differentiation in mesenteric lymph nodes, spleen, and bronchoalveolar lavage cells of mice with bleomycin-induced skin fibrosis. Profibrotic and proinflammatory gene expression was suppressed by SB administration in skin. Furthermore, SB inhibited transforming growth factor β1-responsive proinflammatory expression with increased acetylation of histone 3 in HDFs. Subcutaneous SB application had antifibrogenic effects on the skin. Butyrate ameliorated skin and lung fibrosis by improving anti-inflammatory activity in a mouse model of SSc. Butyrate may exhibit indirect and direct anti-fibrogenic action on fibroblasts by regulating macrophage differentiation and inhibition of histone deacetylase 3. These findings suggest butyrate as an SSc treatment. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:25:41Z |
| publishDate | 2021-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f3f52e14236e476da3b72a298c95cd0c2023-11-21T09:44:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01225276510.3390/ijms22052765Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse ModelsHee Jin Park0Ok-Yi Jeong1Sung Hak Chun2Yun Hong Cheon3Mingyo Kim4Suhee Kim5Sang-Il Lee6Department of Internal Medicine and Institute of Health Science, College of Medicine, Gyeongsang National University and Hospital, Jinju 52727, KoreaDepartment of Internal Medicine and Institute of Health Science, College of Medicine, Gyeongsang National University and Hospital, Jinju 52727, KoreaDepartment of Internal Medicine and Institute of Health Science, College of Medicine, Gyeongsang National University and Hospital, Jinju 52727, KoreaDepartment of Internal Medicine and Institute of Health Science, College of Medicine, Gyeongsang National University and Hospital, Jinju 52727, KoreaDepartment of Internal Medicine and Institute of Health Science, College of Medicine, Gyeongsang National University and Hospital, Jinju 52727, KoreaDepartment of Internal Medicine and Institute of Health Science, College of Medicine, Gyeongsang National University and Hospital, Jinju 52727, KoreaDepartment of Internal Medicine and Institute of Health Science, College of Medicine, Gyeongsang National University and Hospital, Jinju 52727, KoreaSystemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Despite several studies on SSc treatments, effective treatments for SSc are still lacking. Since evidence suggests an association between intestinal microbiota and SSc, we focused on butyrate, which has beneficial effects in autoimmune diseases as a bacterial metabolite. Here, we investigated the therapeutic potential of sodium butyrate (SB) using a bleomycin-induced fibrosis mouse model of SSc and human dermal fibroblasts (HDFs). SB attenuated bleomycin-induced dermal and lung fibrosis in mice. SB influenced fecal microbiota composition (phyla Actinobacteria and Bacteroidetes, genera <i>Bifidobacterium</i> and <i>Ruminococcus_g2</i>). SB controlled macrophage differentiation in mesenteric lymph nodes, spleen, and bronchoalveolar lavage cells of mice with bleomycin-induced skin fibrosis. Profibrotic and proinflammatory gene expression was suppressed by SB administration in skin. Furthermore, SB inhibited transforming growth factor β1-responsive proinflammatory expression with increased acetylation of histone 3 in HDFs. Subcutaneous SB application had antifibrogenic effects on the skin. Butyrate ameliorated skin and lung fibrosis by improving anti-inflammatory activity in a mouse model of SSc. Butyrate may exhibit indirect and direct anti-fibrogenic action on fibroblasts by regulating macrophage differentiation and inhibition of histone deacetylase 3. These findings suggest butyrate as an SSc treatment.https://www.mdpi.com/1422-0067/22/5/2765systemic sclerosisbutyratebleomycinfibrosisfecal microbiota |
| spellingShingle | Hee Jin Park Ok-Yi Jeong Sung Hak Chun Yun Hong Cheon Mingyo Kim Suhee Kim Sang-Il Lee Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models International Journal of Molecular Sciences systemic sclerosis butyrate bleomycin fibrosis fecal microbiota |
| title | Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models |
| title_full | Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models |
| title_fullStr | Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models |
| title_full_unstemmed | Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models |
| title_short | Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models |
| title_sort | butyrate improves skin lung fibrosis and intestinal dysbiosis in bleomycin induced mouse models |
| topic | systemic sclerosis butyrate bleomycin fibrosis fecal microbiota |
| url | https://www.mdpi.com/1422-0067/22/5/2765 |
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