Characterization of Multiple P2X Receptors in Cultured Normal Human Epidermal Keratinocytes

Inoué, Kaori; Denda, Mitsuhiro; Tozaki, Hidetoshi; Fujishita, Kayoko; Koizumi, Schuichi; Inoue, Kazuhide

doi:10.1111/j.0022-202x.2005.23683.x

Cited by 54 publications

(58 citation statements)

References 36 publications

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“…Previous studies in human and rat skin keratinocytes have reported the presence of P2X 2 , P2X 3 , P2X 5 and P2X 7 receptor subunits [23,24]. P2X receptors found in the skin are suggested to have an important physiological role as an initial sensor for external stimuli, and P2X 7 receptors, known to be involved in ATP-induced apoptosis, are likely to participate in the process of the end-stage terminal differentiation of keratinocytes [23]. The presence of P2X receptor expression in epidermal basal cells suggests a potential role for P2X receptors in relation to cell growth and differentiation in the equine hoof.…”

Section: Discussionmentioning

confidence: 91%

“…3 Immunostaining for P2X 1 (a, e), P2X 2 (b, f), P2X 3 (c, g) and P2X 7 to enable it to function in its roles within the suspensory apparatus of the distal phalanx in equids [22]. Previous studies in human and rat skin keratinocytes have reported the presence of P2X 2 , P2X 3 , P2X 5 and P2X 7 receptor subunits [23,24]. P2X receptors found in the skin are suggested to have an important physiological role as an initial sensor for external stimuli, and P2X 7 receptors, known to be involved in ATP-induced apoptosis, are likely to participate in the process of the end-stage terminal differentiation of keratinocytes [23].…”

Section: Discussionmentioning

confidence: 99%

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Distribution of purinergic P2X receptors in the equine digit, cervical spinal cord and dorsal root ganglia

Zamboulis

Senior

Clegg

et al. 2013

Purinergic Signalling

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Purinergic pathways are considered important in pain transmission, and P2X receptors are a key part of this system which has received little attention in the horse. The aim of this study was to identify and characterise the distribution of P2X receptor subtypes in the equine digit and associated vasculature and nervous tissue, including peripheral nerves, dorsal root ganglia and cervical spinal cord, using PCR, Western blot analysis and immunohistochemistry. mRNA signal for most of the tested P2X receptor subunits (P2X 1-5, 7 ) was detected in all sampled equine tissues, whereas P2X 6 receptor subunit was predominantly expressed in the dorsal root ganglia and spinal cord. Western blot analysis validated the specificity of P2X [1][2][3]7 antibodies, and these were used in immunohistochemistry studies. P2X 1-3, 7 receptor subunits were found in smooth muscle cells in the palmar digital artery and vein with the exception of the P2X 3 subunit that was present only in the vein. However, endothelial cells in the palmar digital artery and vein were positive only for P2X 2 and P2X 3 receptor subunits. Neurons and nerve fibres in the peripheral and central nervous system were positive for P2X 1-3 receptor subunits, whereas glial cells were positive for P2X 7 and P2X 1 and 2 receptor subunits. This previously unreported distribution of P2X subtypes may suggest important tissue specific roles in physiological and pathological processes.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Distribution of purinergic P2X receptors in the equine digit, cervical spinal cord and dorsal root ganglia

Zamboulis

Senior

Clegg

et al. 2013

Purinergic Signalling

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“…P2Y1 and P2Y2 receptors expressed in basal layers of the fetal and adult epidermis [111,113] were immune colocalized with the cell proliferation markers Ki67 and PCNA (proliferation cell nuclear antigen) [111]. The P2Y1 receptor agonist 2-methylthio-ADP (P2Y1 agonist) and UTP activating P2Y2 receptors induced proliferation in cell cultures of basal keratinocytes [113].…”

Section: Skin Injurymentioning

confidence: 99%

“…Two important functions are attributed to this nucleotide such as modulation of keratinocyte proliferation and differentiation [110]. Many studies have shown that these effects are mediated by ATP action through P2X and P2Y receptor subtypes, and it is known that the epidermis expresses P2X5, P2X7, P2Y1, and P2Y2 subtypes with diverse functions [111][112][113].…”

Section: Skin Injurymentioning

confidence: 99%

“…The P2Y1 receptor agonist 2-methylthio-ADP (P2Y1 agonist) and UTP activating P2Y2 receptors induced proliferation in cell cultures of basal keratinocytes [113]. P2Y1 and P2Y2 subtypes are coupled to Phospholipase C via G q/11 proteins with generation of Inositol 3-phosphate and, in sequence, induce intracellular calcium mobilization [113] leading to Cl − conductance and starting keratinocyte differentiation [112]. In an in vivo wound-healing model, the P2Y1 receptor is expressed in epidermal basal layers and the wound edge, while the P2Y2 subtype is expressed in basal and suprabasal layers, but is not expressed in the wound edge.…”

Section: Skin Injurymentioning

confidence: 99%

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Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Glaser

Cappellari

Pillat

et al. 2011

Purinergic Signalling

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Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

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Reconstructed human epidermis‐based testing strategy of skin sensitization potential and potency classification using epidermal sensitization assay and in silico data

Mizumachi,

Suzuki,

Sakuma

et al. 2023

J of Applied Toxicology

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The hazards and potency of skin sensitizers are traditionally determined using animal tests such as the local lymph node assay (LLNA); however, significant progress has been made in the development of non‐animal test methods addressing the first three mechanistic key events of adverse outcome pathway in skin sensitization. We developed the epidermal sensitization assay (EpiSensA), which is a reconstructed human epidermis‐based assay, by measuring four genes related to critical keratinocyte responses during skin sensitization. Four in vitro skin sensitization test methods (EpiSensA, direct peptide reactivity assay [DPRA], KeratinoSens™, and human cell line activation test [h‐CLAT]) were systematically evaluated using 136 chemicals including lipophilic chemicals and pre/pro‐haptens, which may be related to assay‐specific limitations. The constructed database included existing and newly generated data. The EpiSensA showed a broader applicability domain and predicted the hazards with 82.4% and 78.8% accuracy than LLNA and human data. The EpiSensA could detect 76 out of 88 sensitizers at lower concentrations than the LLNA, indicating that the EpiSensA has higher sensitivity for the detection of minor sensitizing constituents. These results confirmed the potential use of the EpiSensA in evaluating a mixture of unknown compositions that can be evaluated by animal tests. To combine different information sources, the reconstructed human epidermis‐based testing strategy (RTS) was developed based on weighted multiple information from the EpiSensA and TImes MEtabolism Simulator platform for predicting Skin Sensitization (TIMES‐SS; RTSv1) or Organization for Economic Cooperation and Development (OECD) QSAR Toolbox automated workflow (RTSv2). The predictivities of the hazards and Globally Harmonized System (GHS) subcategories were equal to or better than the defined approaches (2 out of 3, integrated testing strategy [ITS]v1, and ITSv2) adopted as OECD Guideline 497.

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Characterization of Multiple P2X Receptors in Cultured Normal Human Epidermal Keratinocytes

Cited by 54 publications

References 36 publications

Distribution of purinergic P2X receptors in the equine digit, cervical spinal cord and dorsal root ganglia

Distribution of purinergic P2X receptors in the equine digit, cervical spinal cord and dorsal root ganglia

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Reconstructed human epidermis‐based testing strategy of skin sensitization potential and potency classification using epidermal sensitization assay and in silico data

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