Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition

Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Zhao, Pengxiang [verfasserIn] Dang, Zheng Liu, Mengyu Guo, Dazhi Luo, Ruiliu Zhang, Mingzi Xie, Fei Zhang, Xujuan Wang, Youbin Pan, Shuyi Ma, Xuemei

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Molecular hydrogen Wound care Extracellular matrix deposition Epidermal stem cell proliferation Re-epithelialization

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Inflammation and regeneration - London : BioMed Central, part of Springer Nature, 2000, 43(2023), 1 vom: 28. März
Übergeordnetes Werk:	volume:43 ; year:2023 ; number:1 ; day:28 ; month:03

Links:	Volltext

DOI / URN:	10.1186/s41232-023-00271-9

Katalog-ID:	SPR049860879

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520			\|a Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life.
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allfields	10.1186/s41232-023-00271-9 doi (DE-627)SPR049860879 (SPR)s41232-023-00271-9-e DE-627 ger DE-627 rakwb eng Zhao, Pengxiang verfasserin aut Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. Molecular hydrogen (dpeaa)DE-He213 Wound care (dpeaa)DE-He213 Extracellular matrix deposition (dpeaa)DE-He213 Epidermal stem cell proliferation (dpeaa)DE-He213 Re-epithelialization (dpeaa)DE-He213 Dang, Zheng aut Liu, Mengyu aut Guo, Dazhi aut Luo, Ruiliu aut Zhang, Mingzi aut Xie, Fei aut Zhang, Xujuan aut Wang, Youbin aut Pan, Shuyi aut Ma, Xuemei (orcid)0000-0002-9307-066X aut Enthalten in Inflammation and regeneration London : BioMed Central, part of Springer Nature, 2000 43(2023), 1 vom: 28. März (DE-627)559080913 (DE-600)2411877-1 1880-8190 nnns volume:43 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s41232-023-00271-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2023 1 28 03
spelling	10.1186/s41232-023-00271-9 doi (DE-627)SPR049860879 (SPR)s41232-023-00271-9-e DE-627 ger DE-627 rakwb eng Zhao, Pengxiang verfasserin aut Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. Molecular hydrogen (dpeaa)DE-He213 Wound care (dpeaa)DE-He213 Extracellular matrix deposition (dpeaa)DE-He213 Epidermal stem cell proliferation (dpeaa)DE-He213 Re-epithelialization (dpeaa)DE-He213 Dang, Zheng aut Liu, Mengyu aut Guo, Dazhi aut Luo, Ruiliu aut Zhang, Mingzi aut Xie, Fei aut Zhang, Xujuan aut Wang, Youbin aut Pan, Shuyi aut Ma, Xuemei (orcid)0000-0002-9307-066X aut Enthalten in Inflammation and regeneration London : BioMed Central, part of Springer Nature, 2000 43(2023), 1 vom: 28. März (DE-627)559080913 (DE-600)2411877-1 1880-8190 nnns volume:43 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s41232-023-00271-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2023 1 28 03
allfields_unstemmed	10.1186/s41232-023-00271-9 doi (DE-627)SPR049860879 (SPR)s41232-023-00271-9-e DE-627 ger DE-627 rakwb eng Zhao, Pengxiang verfasserin aut Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. Molecular hydrogen (dpeaa)DE-He213 Wound care (dpeaa)DE-He213 Extracellular matrix deposition (dpeaa)DE-He213 Epidermal stem cell proliferation (dpeaa)DE-He213 Re-epithelialization (dpeaa)DE-He213 Dang, Zheng aut Liu, Mengyu aut Guo, Dazhi aut Luo, Ruiliu aut Zhang, Mingzi aut Xie, Fei aut Zhang, Xujuan aut Wang, Youbin aut Pan, Shuyi aut Ma, Xuemei (orcid)0000-0002-9307-066X aut Enthalten in Inflammation and regeneration London : BioMed Central, part of Springer Nature, 2000 43(2023), 1 vom: 28. März (DE-627)559080913 (DE-600)2411877-1 1880-8190 nnns volume:43 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s41232-023-00271-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2023 1 28 03
allfieldsGer	10.1186/s41232-023-00271-9 doi (DE-627)SPR049860879 (SPR)s41232-023-00271-9-e DE-627 ger DE-627 rakwb eng Zhao, Pengxiang verfasserin aut Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. Molecular hydrogen (dpeaa)DE-He213 Wound care (dpeaa)DE-He213 Extracellular matrix deposition (dpeaa)DE-He213 Epidermal stem cell proliferation (dpeaa)DE-He213 Re-epithelialization (dpeaa)DE-He213 Dang, Zheng aut Liu, Mengyu aut Guo, Dazhi aut Luo, Ruiliu aut Zhang, Mingzi aut Xie, Fei aut Zhang, Xujuan aut Wang, Youbin aut Pan, Shuyi aut Ma, Xuemei (orcid)0000-0002-9307-066X aut Enthalten in Inflammation and regeneration London : BioMed Central, part of Springer Nature, 2000 43(2023), 1 vom: 28. März (DE-627)559080913 (DE-600)2411877-1 1880-8190 nnns volume:43 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s41232-023-00271-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2023 1 28 03
allfieldsSound	10.1186/s41232-023-00271-9 doi (DE-627)SPR049860879 (SPR)s41232-023-00271-9-e DE-627 ger DE-627 rakwb eng Zhao, Pengxiang verfasserin aut Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. Molecular hydrogen (dpeaa)DE-He213 Wound care (dpeaa)DE-He213 Extracellular matrix deposition (dpeaa)DE-He213 Epidermal stem cell proliferation (dpeaa)DE-He213 Re-epithelialization (dpeaa)DE-He213 Dang, Zheng aut Liu, Mengyu aut Guo, Dazhi aut Luo, Ruiliu aut Zhang, Mingzi aut Xie, Fei aut Zhang, Xujuan aut Wang, Youbin aut Pan, Shuyi aut Ma, Xuemei (orcid)0000-0002-9307-066X aut Enthalten in Inflammation and regeneration London : BioMed Central, part of Springer Nature, 2000 43(2023), 1 vom: 28. März (DE-627)559080913 (DE-600)2411877-1 1880-8190 nnns volume:43 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s41232-023-00271-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2023 1 28 03
language	English
source	Enthalten in Inflammation and regeneration 43(2023), 1 vom: 28. März volume:43 year:2023 number:1 day:28 month:03
sourceStr	Enthalten in Inflammation and regeneration 43(2023), 1 vom: 28. März volume:43 year:2023 number:1 day:28 month:03
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institution	findex.gbv.de
topic_facet	Molecular hydrogen Wound care Extracellular matrix deposition Epidermal stem cell proliferation Re-epithelialization
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container_title	Inflammation and regeneration
authorswithroles_txt_mv	Zhao, Pengxiang @@aut@@ Dang, Zheng @@aut@@ Liu, Mengyu @@aut@@ Guo, Dazhi @@aut@@ Luo, Ruiliu @@aut@@ Zhang, Mingzi @@aut@@ Xie, Fei @@aut@@ Zhang, Xujuan @@aut@@ Wang, Youbin @@aut@@ Pan, Shuyi @@aut@@ Ma, Xuemei @@aut@@
publishDateDaySort_date	2023-03-28T00:00:00Z
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While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. 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topic_title	Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition Molecular hydrogen (dpeaa)DE-He213 Wound care (dpeaa)DE-He213 Extracellular matrix deposition (dpeaa)DE-He213 Epidermal stem cell proliferation (dpeaa)DE-He213 Re-epithelialization (dpeaa)DE-He213
topic	misc Molecular hydrogen misc Wound care misc Extracellular matrix deposition misc Epidermal stem cell proliferation misc Re-epithelialization
topic_unstemmed	misc Molecular hydrogen misc Wound care misc Extracellular matrix deposition misc Epidermal stem cell proliferation misc Re-epithelialization
topic_browse	misc Molecular hydrogen misc Wound care misc Extracellular matrix deposition misc Epidermal stem cell proliferation misc Re-epithelialization
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title	Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition
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title_full	Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition
author_sort	Zhao, Pengxiang
journal	Inflammation and regeneration
journalStr	Inflammation and regeneration
lang_code	eng
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author_browse	Zhao, Pengxiang Dang, Zheng Liu, Mengyu Guo, Dazhi Luo, Ruiliu Zhang, Mingzi Xie, Fei Zhang, Xujuan Wang, Youbin Pan, Shuyi Ma, Xuemei
container_volume	43
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author-letter	Zhao, Pengxiang
doi_str_mv	10.1186/s41232-023-00271-9
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title_sort	molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition
title_auth	Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition
abstract	Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. © The Author(s) 2023
abstractGer	Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. © The Author(s) 2023
abstract_unstemmed	Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. $ H_{2} $ has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how $ H_{2} $ functions in wound healing remains unknown, especially for the link between $ H_{2} $ and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of $ H_{2} $ (66% $ H_{2} $) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of $ H_{2} $ (66% $ H_{2} $) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on $ O_{2} $ or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the $ H_{2} $ group. ECM components early (3 days post-wounding) deposition were found in the $ H_{2} $ group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. $ H_{2} $ accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between $ H_{2} $ and ECM deposition and EpSCs activation. These $ H_{2} $-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life. © The Author(s) 2023
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title_short	Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition
url	https://dx.doi.org/10.1186/s41232-023-00271-9
remote_bool	true
author2	Dang, Zheng Liu, Mengyu Guo, Dazhi Luo, Ruiliu Zhang, Mingzi Xie, Fei Zhang, Xujuan Wang, Youbin Pan, Shuyi Ma, Xuemei
author2Str	Dang, Zheng Liu, Mengyu Guo, Dazhi Luo, Ruiliu Zhang, Mingzi Xie, Fei Zhang, Xujuan Wang, Youbin Pan, Shuyi Ma, Xuemei
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up_date	2024-07-04T02:34:27.690Z
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