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

IF 5 3区 医学 Q2 IMMUNOLOGY Inflammation and Regeneration Pub Date : 2023-03-28 DOI:10.1186/s41232-023-00271-9
Pengxiang Zhao, Zheng Dang, Mengyu Liu, Dazhi Guo, Ruiliu Luo, Mingzi Zhang, Fei Xie, Xujuan Zhang, Youbin Wang, Shuyi Pan, Xuemei Ma
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引用次数: 4

Abstract

Background: Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H2 has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H2 functions in wound healing remains unknown, especially for the link between H2 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 H2 (66% H2) 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 H2 (66% H2) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on O2 or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H2 group. ECM components early (3 days post-wounding) deposition were found in the H2 group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H2 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 H2 and ECM deposition and EpSCs activation. These H2-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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氢分子通过诱导早期表皮干细胞增殖和细胞外基质沉积促进创面愈合。
背景:尽管伤口护理策略的发展取得了进展,但目前还没有能够促进自组织修复能力的治疗方法。H2已被证明可以有效地保护细胞和组织免受氧化和炎症损伤。然而,H2在伤口愈合中的综合作用和功能尚不清楚,特别是H2与细胞外基质(ECM)沉积和表皮干细胞(EpSCs)活化之间的联系。方法:建立皮肤无菌创面模型,在治疗室中应用高浓度H2 (66% H2)。通过基因功能富集分析、数字空间谱仪分析、血液灌注/氧检测、体外试管形成实验、酶联免疫吸附实验、免疫荧光染色、非靶向代谢组学分析、流式细胞术、透射电镜和活细胞成像来评估分子机制和愈合效果。结果:我们发现高浓度H2 (66% H2)在损伤后第11天显著提高了愈合率(比对照组高3倍)。效果不依赖于O2或抗活性氧功能。组织学和细胞实验证实H2组的再上皮化速度较快。创面H2组早期(伤后3 d)有ECM成分沉积,尤其是真皮col- 1、表皮col-III和真皮-表皮交界处col-XVII。H2加速了早期自体EpSCs的增殖(提前1-2天)并向肌上皮细胞分化。这些表皮肌上皮细胞可能进一步促进ECM沉积。其他有益的结果包括持续的湿润愈合,更大的血管化,更少的T-helper-1和T-helper-17细胞相关的全身炎症,以及更好的组织重塑。结论:我们发现了一种分子氢诱导伤口愈合的新模式。这是首次揭示H2和ECM沉积与EpSCs激活之间的直接联系。这些h2诱导的愈合的多重优势可能与在生命的生物过程中提高各种细胞的活力和在基本水平上维持线粒体功能有关。
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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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