The Local Neuropeptide System of Keratinocytes

Cirillo, Nicola

doi:10.3390/biomedicines9121854

Cited by 11 publications

(12 citation statements)

References 80 publications

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“…β-endorphin has a local effect for pain management [ 140 ]. α-MSH serves locally to stimulate melanocytes for pigment production and regulate inflammation and extracellular matrix homeostasis through the receptor MC1R [ 141 ]. The other protein and non-protein groups reflect single reports of non-related secretions, including hyaluronan, which is an important component of the extracellular matrix.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

El‐Serafi

El-Serafi

Steinvall

et al. 2022

IJMS

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Cell regenerative therapy is a modern solution for difficult-to-heal wounds. Keratinocytes, the most common cell type in the skin, are difficult to obtain without the creation of another wound. Stem cell differentiation towards keratinocytes is a challenging process, and it is difficult to reproduce in chemically defined media. Nevertheless, a co-culture of keratinocytes with stem cells usually achieves efficient differentiation. This systematic review aims to identify the secretions of normal human keratinocytes reported in the literature and correlate them with the differentiation process. An online search revealed 338 references, of which 100 met the selection criteria. A total of 80 different keratinocyte secretions were reported, which can be grouped mainly into cytokines, growth factors, and antimicrobial peptides. The growth-factor group mostly affects stem cell differentiation into keratinocytes, especially epidermal growth factor and members of the transforming growth factor family. Nevertheless, the reported secretions reflected the nature of the involved studies, as most of them focused on keratinocyte interaction with inflammation. This review highlights the secretory function of keratinocytes, as well as the need for intense investigation to characterize these secretions and evaluate their regenerative capacities.

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Section: Resultsmentioning

confidence: 99%

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

El‐Serafi

El-Serafi

Steinvall

et al. 2022

IJMS

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“…Skin is considered as an important peripheral neuro-endocrine-immune organ closely linked to the central regulatory systems. The local synthesis of neuropeptides also takes place in keratinocytes ( 24 ). Thus, we further examined the expression of neuropeptides in keratinocytes, showing that glutamic acid or aspartic acid induced elevation of VIP , PACAP , CGRP α , and CGRP β in HaCaT keratinocytes in a dose-dependent manner ( Figure 5, C and D ), whereas leucine did not increase the expression of neuropeptides ( Supplemental Figure 4C ).…”

Section: Resultsmentioning

confidence: 99%

“…We speculated that the expression of VIP induced by amino acids could be an important cause of neurogenic vasodilation in rosacea. In addition, evidence for a neuropeptidergic system in skin keratinocytes was reported ( 24 ). Here, we demonstrated that VIP , PACAP , CGRP α , and CGRP β , mediating angiogenesis and vasodilation in skin, were all upregulated in keratinocytes by glutamic acid and aspartic acid.…”

Section: Discussionmentioning

confidence: 99%

Aberrant amino acid metabolism promotes neurovascular reactivity in rosacea

Liu¹,

Xiao²,

Chen³

et al. 2022

JCI Insight

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Rosacea is a chronic skin disorder characterized by abnormal neurovascular and inflammatory conditions on the central face. Despite increasing evidence suggests that rosacea is associated with metabolic disorders, the role of metabolism in rosacea pathogenesis remains unknown. Here, via targeted metabolomics approach, we characterized significantly altered metabolic signatures in rosacea patients, especially for amino acid-related metabolic pathways. Among these, glutamic acid and aspartic acid are highlighted and positively correlated with the disease severity in rosacea patients. We further demonstrated that glutamic acid and aspartic acid can facilitate the development of erythema and telangiectasia, typical features of rosacea, in the skin of mice. Mechanistically, glutamic acid and aspartic acid stimulate the production of vasodilation-related neuropeptides from peripheral neuron and keratinocytes, and induce the release of nitric oxide from endothelial cells and keratinocytes. Interestingly, we provided evidence showing that doxycycline can improve the symptoms of rosacea patients possibly by targeting amino acid metabolic pathway. These findings reveal that abnormal amino acid metabolism promotes neurovascular reactivity in rosacea, and raise the possibility of targeting dysregulated metabolism as a promising strategy for clinical treatment.

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“…The endogenous opioid system consists of neuropeptides (endorphins, enkephalins, endomorphins, and dynorphins) and opioid receptors (ORs, µ, δ, and κ) (Cirillo, 2021). δ-OR, κ-OR, µ-OR, and nociceptin/orphanin FQ peptide receptor (NOP) are expressed on KCs (Bigliardi et al, 1998(Bigliardi et al, , 2015Andoh et al, 2004;Tominaga et al, 2007).…”

Section: Endogenous Opioid Systemmentioning

confidence: 99%

Emerging roles of keratinocytes in nociceptive transduction and regulation

Yu²,

Xu³

et al. 2022

Front. Mol. Neurosci.

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Keratinocytes are the predominant block-building cells in the epidermis. Emerging evidence has elucidated the roles of keratinocytes in a wide range of pathophysiological processes including cutaneous nociception, pruritus, and inflammation. Intraepidermal free nerve endings are entirely enwrapped within the gutters of keratinocyte cytoplasm and form en passant synaptic-like contacts with keratinocytes. Keratinocytes can detect thermal, mechanical, and chemical stimuli through transient receptor potential ion channels and other sensory receptors. The activated keratinocytes elicit calcium influx and release ATP, which binds to P2 receptors on free nerve endings and excites sensory neurons. This process is modulated by the endogenous opioid system and endothelin. Keratinocytes also express neurotransmitter receptors of adrenaline, acetylcholine, glutamate, and γ-aminobutyric acid, which are involved in regulating the activation and migration, of keratinocytes. Furthermore, keratinocytes serve as both sources and targets of neurotrophic factors, pro-inflammatory cytokines, and neuropeptides. The autocrine and/or paracrine mechanisms of these mediators create a bidirectional feedback loop that amplifies neuroinflammation and contributes to peripheral sensitization.

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The Local Neuropeptide System of Keratinocytes

Cited by 11 publications

References 80 publications

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

Aberrant amino acid metabolism promotes neurovascular reactivity in rosacea

Emerging roles of keratinocytes in nociceptive transduction and regulation

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