SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically
Abstract Objectives To investigate the effects of suberoylanilide hydroxamic acid (SAHA) on lung fibroblast activation and to examine the role of p66Shc in this process. Methods An in vitro pulmonary fibrosis model was established using transforming growth factor‐β (TGF‐β)‐induced MRC‐5 lung fibrobl...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Aging Medicine |
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| Online Access: | https://doi.org/10.1002/agm2.12385 |
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| author | Yiheng Dong Jieting Peng Xiangyu Zhang Qiong Wang Xing Lyu |
| author_facet | Yiheng Dong Jieting Peng Xiangyu Zhang Qiong Wang Xing Lyu |
| author_sort | Yiheng Dong |
| collection | DOAJ |
| description | Abstract Objectives To investigate the effects of suberoylanilide hydroxamic acid (SAHA) on lung fibroblast activation and to examine the role of p66Shc in this process. Methods An in vitro pulmonary fibrosis model was established using transforming growth factor‐β (TGF‐β)‐induced MRC‐5 lung fibroblasts. The proliferation and migration capacities of MRC‐5 cells, along with the expression of fibrosis‐related genes, were assessed following treatment with SAHA and/or silence of p66Shc. Results In TGF‐β‐induced MRC‐5 lung fibroblasts, SAHA treatment significantly inhibited cell proliferation and migration, as well as the expression of fibrosis‐related genes, including collagen I and α‐smooth muscle actin (SMA). Western blot and immunofluorescence assays revealed that SAHA increased p66Shc expression in both whole cells and mitochondria. Additionally, mito‐SOX assay confirmed that SAHA treatment led to a marked accumulation of mitochondrial reactive oxygen species (ROS). However, silencing of p66Shc significantly reversed the aforementioned effects of SAHA on MRC‐5 cells. Furthermore, chromatin immunoprecipitation (ChIP) assays demonstrated that SAHA enhanced active histone markers, H3K9Ac and H3K4Me3, in the p66Shc gene region. Conclusions SAHA alleviates lung fibroblast activation and migration by increasing p66Shc expression and mitochondrial ROS generation through epigenetic modifications of histone 3. |
| format | Article |
| id | doaj-art-ced869726bb34fc1b33f8ba8ea7f37f8 |
| institution | Kabale University |
| issn | 2475-0360 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Aging Medicine |
| spelling | doaj-art-ced869726bb34fc1b33f8ba8ea7f37f82025-01-04T08:39:02ZengWileyAging Medicine2475-03602024-12-017679080110.1002/agm2.12385SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigeneticallyYiheng Dong0Jieting Peng1Xiangyu Zhang2Qiong Wang3Xing Lyu4Department of Geriatrics The Second Xiangya Hospital, Central South University Changsha Hunan ChinaDepartment of Geriatric Respiratory and Sleep The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou Henan ChinaDepartment of Geriatrics The Second Xiangya Hospital, Central South University Changsha Hunan ChinaDepartment of Geriatrics The Second Xiangya Hospital, Central South University Changsha Hunan ChinaDepartment of Laboratory Medicine The Second Xiangya Hospital, Central South University Changsha Hunan ChinaAbstract Objectives To investigate the effects of suberoylanilide hydroxamic acid (SAHA) on lung fibroblast activation and to examine the role of p66Shc in this process. Methods An in vitro pulmonary fibrosis model was established using transforming growth factor‐β (TGF‐β)‐induced MRC‐5 lung fibroblasts. The proliferation and migration capacities of MRC‐5 cells, along with the expression of fibrosis‐related genes, were assessed following treatment with SAHA and/or silence of p66Shc. Results In TGF‐β‐induced MRC‐5 lung fibroblasts, SAHA treatment significantly inhibited cell proliferation and migration, as well as the expression of fibrosis‐related genes, including collagen I and α‐smooth muscle actin (SMA). Western blot and immunofluorescence assays revealed that SAHA increased p66Shc expression in both whole cells and mitochondria. Additionally, mito‐SOX assay confirmed that SAHA treatment led to a marked accumulation of mitochondrial reactive oxygen species (ROS). However, silencing of p66Shc significantly reversed the aforementioned effects of SAHA on MRC‐5 cells. Furthermore, chromatin immunoprecipitation (ChIP) assays demonstrated that SAHA enhanced active histone markers, H3K9Ac and H3K4Me3, in the p66Shc gene region. Conclusions SAHA alleviates lung fibroblast activation and migration by increasing p66Shc expression and mitochondrial ROS generation through epigenetic modifications of histone 3.https://doi.org/10.1002/agm2.12385histone modificationlung fibroblastsp66Shcpulmonary fibrosisSAHA |
| spellingShingle | Yiheng Dong Jieting Peng Xiangyu Zhang Qiong Wang Xing Lyu SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically Aging Medicine histone modification lung fibroblasts p66Shc pulmonary fibrosis SAHA |
| title | SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically |
| title_full | SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically |
| title_fullStr | SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically |
| title_full_unstemmed | SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically |
| title_short | SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically |
| title_sort | saha inhibits lung fibroblast activation by increasing p66shc expression epigenetically |
| topic | histone modification lung fibroblasts p66Shc pulmonary fibrosis SAHA |
| url | https://doi.org/10.1002/agm2.12385 |
| work_keys_str_mv | AT yihengdong sahainhibitslungfibroblastactivationbyincreasingp66shcexpressionepigenetically AT jietingpeng sahainhibitslungfibroblastactivationbyincreasingp66shcexpressionepigenetically AT xiangyuzhang sahainhibitslungfibroblastactivationbyincreasingp66shcexpressionepigenetically AT qiongwang sahainhibitslungfibroblastactivationbyincreasingp66shcexpressionepigenetically AT xinglyu sahainhibitslungfibroblastactivationbyincreasingp66shcexpressionepigenetically |