Modulation of biological activities in adipose derived stem cells by histone deacetylation

Abstract Difficult-to-heal wounds management accounts for about 4% of healthcare costs, highlighting the need for innovative solutions. Extracellular signals drive cell proliferation during tissue regeneration, while epigenetic mechanisms regulate stem cell homeostasis, differentiation, and skin rep...

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Main Authors: Sallam Abdallah, Mouna Tabebi, Sawsan Qanadilo, Neserin Ali, Jing Wang, Pádraig D’Arcy, Wen Zhong, Folke Sjoberg, Moustafa Elmasry, Ahmed El-Serafi
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Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84652-1
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author Sallam Abdallah
Mouna Tabebi
Sawsan Qanadilo
Neserin Ali
Jing Wang
Pádraig D’Arcy
Wen Zhong
Folke Sjoberg
Moustafa Elmasry
Ahmed El-Serafi
author_facet Sallam Abdallah
Mouna Tabebi
Sawsan Qanadilo
Neserin Ali
Jing Wang
Pádraig D’Arcy
Wen Zhong
Folke Sjoberg
Moustafa Elmasry
Ahmed El-Serafi
author_sort Sallam Abdallah
collection DOAJ
description Abstract Difficult-to-heal wounds management accounts for about 4% of healthcare costs, highlighting the need for innovative solutions. Extracellular signals drive cell proliferation during tissue regeneration, while epigenetic mechanisms regulate stem cell homeostasis, differentiation, and skin repair. Exploring epigenetic regulation in adipose-derived stem cells (ADSCs) holds promise for improving skin injury treatments. We investigated the effects of histone deacetylase inhibitor (SAHA) on ADSCs to better understand its cellular and molecular impacts. ADSCs were treated with SAHA for 72 h, showing no change in cell viability at the studied concentrations. However, the expression of histone deacetylase decreased at 1000 nM, while the cell proliferation marker Ki-67 increased after SAHA treatment, as confirmed by immunofluorescence. CCND1 gene expression increased, whereas protein expression of the proliferating cell nuclear antigen (PCNA) decreased. Cell cycle analysis showed an increase in G2 phase in SAHA-treated cells. Microarray analysis revealed 74 upregulated and 40 downregulated differentially expressed genes, including upregulation of P53 targets, CDKN1A and MDM2. Proteomic analysis identified 631 upregulated and 823 downregulated proteins compared to the vehicle. Pathway enrichment analysis showed cell cycle, ATP-dependent chromatin remodeling and DNA processes were among the affected pathways. This study suggests SAHA modulates ADSCs’ biological processes, highlighting its potential for skin regeneration.
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spelling doaj-art-bb703cbf8e1f4da791dcf838ed201f2e2025-02-02T12:16:45ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-024-84652-1Modulation of biological activities in adipose derived stem cells by histone deacetylationSallam Abdallah0Mouna Tabebi1Sawsan Qanadilo2Neserin Ali3Jing Wang4Pádraig D’Arcy5Wen Zhong6Folke Sjoberg7Moustafa Elmasry8Ahmed El-Serafi9The Department of Biomedical and Clinical Sciences (BKV), Linköping UniversityThe Department of Biomedical and Clinical Sciences (BKV), Linköping UniversityDepartment of Biological Sciences, The University of JordanDepartment of Clinical Sciences, Lund UniversityThe Department of Biomedical and Clinical Sciences (BKV), Linköping UniversityThe Department of Biomedical and Clinical Sciences (BKV), Linköping UniversityThe Department of Biomedical and Clinical Sciences (BKV), Linköping UniversityThe Department of Biomedical and Clinical Sciences (BKV), Linköping UniversityThe Department of Biomedical and Clinical Sciences (BKV), Linköping UniversityThe Department of Biomedical and Clinical Sciences (BKV), Linköping UniversityAbstract Difficult-to-heal wounds management accounts for about 4% of healthcare costs, highlighting the need for innovative solutions. Extracellular signals drive cell proliferation during tissue regeneration, while epigenetic mechanisms regulate stem cell homeostasis, differentiation, and skin repair. Exploring epigenetic regulation in adipose-derived stem cells (ADSCs) holds promise for improving skin injury treatments. We investigated the effects of histone deacetylase inhibitor (SAHA) on ADSCs to better understand its cellular and molecular impacts. ADSCs were treated with SAHA for 72 h, showing no change in cell viability at the studied concentrations. However, the expression of histone deacetylase decreased at 1000 nM, while the cell proliferation marker Ki-67 increased after SAHA treatment, as confirmed by immunofluorescence. CCND1 gene expression increased, whereas protein expression of the proliferating cell nuclear antigen (PCNA) decreased. Cell cycle analysis showed an increase in G2 phase in SAHA-treated cells. Microarray analysis revealed 74 upregulated and 40 downregulated differentially expressed genes, including upregulation of P53 targets, CDKN1A and MDM2. Proteomic analysis identified 631 upregulated and 823 downregulated proteins compared to the vehicle. Pathway enrichment analysis showed cell cycle, ATP-dependent chromatin remodeling and DNA processes were among the affected pathways. This study suggests SAHA modulates ADSCs’ biological processes, highlighting its potential for skin regeneration.https://doi.org/10.1038/s41598-024-84652-1Histone deacetylase inhibitorSuberoylanilide hydroxamic acidAdipose derived stem cellsDifferentiationVorinostatEpigenetic
spellingShingle Sallam Abdallah
Mouna Tabebi
Sawsan Qanadilo
Neserin Ali
Jing Wang
Pádraig D’Arcy
Wen Zhong
Folke Sjoberg
Moustafa Elmasry
Ahmed El-Serafi
Modulation of biological activities in adipose derived stem cells by histone deacetylation
Scientific Reports
Histone deacetylase inhibitor
Suberoylanilide hydroxamic acid
Adipose derived stem cells
Differentiation
Vorinostat
Epigenetic
title Modulation of biological activities in adipose derived stem cells by histone deacetylation
title_full Modulation of biological activities in adipose derived stem cells by histone deacetylation
title_fullStr Modulation of biological activities in adipose derived stem cells by histone deacetylation
title_full_unstemmed Modulation of biological activities in adipose derived stem cells by histone deacetylation
title_short Modulation of biological activities in adipose derived stem cells by histone deacetylation
title_sort modulation of biological activities in adipose derived stem cells by histone deacetylation
topic Histone deacetylase inhibitor
Suberoylanilide hydroxamic acid
Adipose derived stem cells
Differentiation
Vorinostat
Epigenetic
url https://doi.org/10.1038/s41598-024-84652-1
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