Characteristics and roles of extracellular vesicles released by epidermal keratinocytes

Than, Uyen Thi Trang; Leavesley, David I.; Parker, Tony J.

doi:10.1111/jdv.15859

Cited by 29 publications

(16 citation statements)

References 72 publications

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“…Keratinocyte EV secretion is induced by various stimuli, such as hypoxia, irradiation, and starvation. Increasing evidence depicts that keratinocyte-derived EVs play a role in the wound healing process [ 79 , 80 ]. Keratinocyte-derived exosomes can affect the dendritic cell phenotype and cytokine production [ 81 ].…”

Section: Crosstalk Between Keratinocytes and Immune Cells During Smentioning

confidence: 99%

The Immune Functions of Keratinocytes in Skin Wound Healing

Piipponen

Landén

2020

IJMS

250

139

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As the most dominant cell type in the skin, keratinocytes play critical roles in wound repair not only as structural cells but also exerting important immune functions. This review focuses on the communications between keratinocytes and immune cells in wound healing, which are mediated by various cytokines, chemokines, and extracellular vesicles. Keratinocytes can also directly interact with T cells via antigen presentation. Moreover, keratinocytes produce antimicrobial peptides that can directly kill the invading pathogens and contribute to wound repair in many aspects. We also reviewed the epigenetic mechanisms known to regulate keratinocyte immune functions, including histone modifications, non-protein-coding RNAs (e.g., microRNAs, and long noncoding RNAs), and chromatin dynamics. Lastly, we summarized the current evidence on the dysregulated immune functions of keratinocytes in chronic nonhealing wounds. Based on their crucial immune functions in skin wound healing, we propose that keratinocytes significantly contribute to the pathogenesis of chronic wound inflammation. We hope this review will trigger an interest in investigating the immune roles of keratinocytes in chronic wound pathology, which may open up new avenues for developing innovative wound treatments.

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Section: Crosstalk Between Keratinocytes and Immune Cells During Smentioning

confidence: 99%

The Immune Functions of Keratinocytes in Skin Wound Healing

Piipponen

Landén

2020

IJMS

250

139

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“…EVs have been shown to transfer information between cells [29]. Our proteomic analysis findings show that EV-derived proteins strongly associated with the MAP-Kinase pathway (Fig.…”

Section: The Mapkinase Pathway Is Activated By Evsmentioning

confidence: 66%

Human keratinocyte-derived extracellular vesicles activate the MAPKinase pathway and promote cell migration and proliferation in vitro

2021

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Background Wound healing is a complex biological process and complete skin regeneration is still a critical challenge. Extracellular vesicles (EVs) play essential roles in cell communication and cell regeneration, and recent studies have suggested that EVs may contribute to wound healing, though the molecular mechanisms behind this contribution remain unclear. For these reasons, we decided to use EVs isolated from human keratinocytes (HaCaT) in vitro to determine the potential mechanism of action of EV-derived wound healing. Method Scratch assays were used to determine cell migration and proliferation. Scratched cells were exposed to EVs in multiple conditions to determine how they affect wound healing. Statistical analysis between groups was carried out to using Student’s two-sided t test. A p value of < 0.05 was considered statistically significant. Result We found that proteomic analysis of purified EVs shows enrichment of proteins associated with cell communication and signal transduction, such as MAPK pathways, and keratinocyte and fibroblast cultures exposed to EVs had higher levels of proliferation, migration, and ERK1/2 and P38 activation. Moreover, we found that treatment with specific ERK1/2 and P38 signaling inhibitors PD98059 and SB239063 impaired EV-mediated cell migration, which suggests that ERK1/2 and P38 signaling is essential for EV-induced wound healing. Conclusion HaCaT cell-derived EVs accelerate the migration and proliferation of human keratinocytes and fibroblasts and may promote wound healing via the activation of MAPKinase pathways. These findings may be key in developing new methods to treat wounds and accelerate wound healing in the future.

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“… 5 , 11 For instance, keratinocytes which make up 90% of the cells in the epidermis, can communicate with other skin cells such as fibroblasts, melanocytes and immune cells through EVs. 12 , 13 It was also reported that keratinocyte-EVs can stimulate the expression of metalloproteinase-1 (MMP1) in dermal fibroblasts to modify the ECM. 12 In addition, keratinocyte-EVs and human immortalized keratinocyte (HaCaT)-EVs stimulate fibroblasts migration and induce fibroblast-mediated endothelial tube formation by activating the ERK1/2, JNK, Smad, and p38 signaling pathways, hence mediating wound healing.…”

Section: Skin and Skin Derived Extracellular Vesiclesmentioning

confidence: 99%

“… 12 , 13 It was also reported that keratinocyte-EVs can stimulate the expression of metalloproteinase-1 (MMP1) in dermal fibroblasts to modify the ECM. 12 In addition, keratinocyte-EVs and human immortalized keratinocyte (HaCaT)-EVs stimulate fibroblasts migration and induce fibroblast-mediated endothelial tube formation by activating the ERK1/2, JNK, Smad, and p38 signaling pathways, hence mediating wound healing. 14 Moreover, keratinocyte-EVs can affect other keratinocytes, macrophages, dendritic cells and neutrophils during skin inflammation.…”

Section: Skin and Skin Derived Extracellular Vesiclesmentioning

confidence: 99%

Extracellular Vesicles: Emerging Therapeutics in Cutaneous Lesions

Xiao

Tang

et al. 2021

IJN

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Extracellular vesicles (EVs), as nanoscale membranous vesicles containing DNAs, RNAs, lipids and proteins, have emerged as promising diagnostic and therapeutic agents for skin diseases. Here, we summarize the basic physiology of the skin and the biological characteristic of EVs. Further, we describe the applications of EVs in the treatment of dermatological conditions such as skin infection, inflammatory skin diseases, skin repair and rejuvenation and skin cancer. In particular, plant-derived EVs and clinical trials are discussed. In addition, challenges and perspectives related to the preclinical and clinical applications of EVs are highlighted.

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Characteristics and roles of extracellular vesicles released by epidermal keratinocytes

Cited by 29 publications

References 72 publications

The Immune Functions of Keratinocytes in Skin Wound Healing

The Immune Functions of Keratinocytes in Skin Wound Healing

Human keratinocyte-derived extracellular vesicles activate the MAPKinase pathway and promote cell migration and proliferation in vitro

Extracellular Vesicles: Emerging Therapeutics in Cutaneous Lesions

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