Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization

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Abstract

The skin, which serves as the first barrier of the human body, is particularly susceptible to exogenous injuries. Skin wounds, including acute burns and chronic non-healing ulcers, are commonly observed in clinics. Healing of skin wounds is a complex process, consisting of infiltration of inflammatory cells, cellular proliferation, and tissue remodeling phases, which restore the integrity and functions of the skin. Epithelialization is involved in wound healing through re-establishing an intact keratinocyte layer. Epidermal stem cells are indispensable for epithelialization, and they are regulated by multiple proinflammatory cytokines or growth factors. In this review, we summarize recent advances in the effect of these cytokines on migration, proliferation, and differentiation processes of epidermal stem cells. We also introduce promising therapeutic strategies targeting epidermal stem cells or related proinflammatory cytokines for patients with skin wounds.

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Most cited references 57

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Wound Healing: A Cellular Perspective

Melanie Rodrigues, Nina Kosaric, Clark Bonham … (2019)

Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis, inflammation, growth, re-epithelialization, and remodeling. With the evolution of single cell technologies, it has been possible to uncover phenotypic and functional heterogeneity within several of these cell types. There have also been discoveries of rare, stem cell subsets within the skin, which are unipotent in the uninjured state, but become multipotent following skin injury. Unraveling the roles of each of these cell types and their interactions with each other is important in understanding the mechanisms of normal wound closure. Changes in the microenvironment including alterations in mechanical forces, oxygen levels, chemokines, extracellular matrix and growth factor synthesis directly impact cellular recruitment and activation, leading to impaired states of wound healing. Single cell technologies can be used to decipher these cellular alterations in diseased states such as in chronic wounds and hypertrophic scarring so that effective therapeutic solutions for healing wounds can be developed.

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Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing

Satish Patel, Shikha Srivastava, Manju Rawat Singh … (2019)

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Inflammatory Memory Sensitizes Skin Epithelial Stem Cells to Tissue Damage

Shruti Naik, Samantha Larsen, Nicholas C. Gomez … (2017)

Summary The body’s first line of defense against environmental assaults, the skin barrier is maintained by epithelial stem cells (EpSCs). Despite EpSCs’ vulnerability to inflammatory pressures, neither the primary response nor its enduring consequences are understood. Here, we unearth a prolonged memory to acute inflammation that enables EpSCs to hasten barrier restoration following subsequent tissue damage. This functional adaptation does not require skin resident macrophages or T cells. Rather, EpSCs maintain chromosomal accessibility at key stress response genes that are activated by the primary stimulus. Upon a secondary challenge, genes governed by these domains are transcribed rapidly. Fueling this memory is Aim2, encoding an activator of the inflammasome. Absence of AIM2 or its downstream effectors, Caspase-1 and Interleukin-1β, erases EpSCs’ ability to recollect inflammation. While EpSCs benefit from inflammatory tuning by heightening their responsiveness to subsequent stressors, this enhanced sensitivity likely increases their susceptibility to autoimmune and hyperproliferative disorders, including cancer.

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Author and article information

Contributors

Yumin Xia:

ORCID: http://orcid.org/0000-0002-3493-7198

xiayumin1202@163.com

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 11 June 2020

Publication date PMC-release: 11 June 2020

Publication date Collection: 2020

Volume: 11

Electronic Location Identifier: 232

Affiliations

GRID grid.452672.0, Department of Dermatology, , The Second Affiliated Hospital of Xi’an Jiaotong University, ; 157 Xiwu Road, Xi’an, 710004 China

Author information

Yumin Xia http://orcid.org/0000-0002-3493-7198

Article

Publisher ID: 1755

DOI: 10.1186/s13287-020-01755-y

PMC ID: 7291661

PubMed ID: 32527289

SO-VID: c16dbe5d-3d4e-4bd4-87e6-c225566aa94e

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 30 April 2020

Date revision received : 28 May 2020

Date accepted : 1 June 2020

Funding

Funded by: The National Natural Science Foundation of China

Award ID: No.81630081

Award Recipient : Yumin Xia

Funded by: The Innovation Capability Support Plan of Shaanxi Province

Award ID: No.2019TD-034

Award Recipient : Yumin Xia

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ScienceOpen disciplines: Molecular medicine

Keywords: epidermal stem cell,epithelialization,proinflammatory cytokine,skin,wound healing

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ScienceOpen disciplines: Molecular medicine

Keywords: epidermal stem cell, epithelialization, proinflammatory cytokine, skin, wound healing

Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization

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Abstract

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Stress signalling in stem cells

Most cited references 57

Wound Healing: A Cellular Perspective

Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing

Inflammatory Memory Sensitizes Skin Epithelial Stem Cells to Tissue Damage

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