Genji Imokawa's research while affiliated with Utsunomiya University and other places
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Publications (244)
β-Sitosterol 3- O - d -glucoside (BSG) is known to act as an agonist by binding to estrogen receptors, and estrogen has been reported to enhance the activity of β-glucocerebrosidase, an epidermal ceramide metabolizing enzyme. In this study, we determined whether BSG up-regulates ceramide levels in the stratum corneum (SC) of a reconstructed human e...
Little is known about the effects on hyaluronan (HA) metabolism of UVA radiation. This study demonstrates that the secretion of HA by human dermal fibroblasts (HDFs) is downregulated by UVA, accompanied by the down- and upregulation of mRNA and protein levels of the HA-synthesizing enzyme (HAS2) and the HA-degrading protein, HYaluronan Binding prot...
![Figure 5. Percent recovery in TEWL values following tape-stripping [21].](publication/349069029/figure/fig5/AS:988044282830848@1612579522690/Percent-recovery-in-TEWL-values-following-tape-stripping-21_Q320.jpg)
Atopic dermatitis (AD) is characterized clinically by severe dry skin and functionally by both a cutaneous barrier disruption and an impaired water-holding capacity in the stratum corneum (SC) even in the nonlesional skin. The combination of the disrupted barrier and water-holding functions in nonlesional skin is closely linked to the disease sever...
A ceramide deficiency in the stratum corneum (SC) is an essential etiologic factor for the dry and barrier-disrupted skin of patients with atopic dermatitis (AD). Previously, we reported that sphingomyelin (SM) deacylase, which hydrolyzes SM and glucosylceramide at the acyl site to yield their lysoforms sphingosylphosphorylcholine (SPC) and glucosy...
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that critically supports the physicochemical and mechanical properties of the skin. Here, we demonstrate that mycosporine-like amino acids (MAAs), which typically function as UV-absorbing compounds, can stimulate HA secretion from normal human fibroblasts. MAA-stimulated HA secretion was...
Little is known about the pathophysiological linkages between altered ceramide profiles in the stratum corneum (SC) of patients with atopic dermatitis (AD) and their impaired skin barrier and water-holding functions. We studied those characteristics following topical treatment with a designed synthetic pseudo-ceramide (pCer) and analyzed that patho...
To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1/endothelin B receptors (EDNBRs), stem cell factor (SCF)/c-KIT, and tumor necrosis factor (TNF)α in the lesional epidermis, which contrasted with the downr...
Little is known about the anti-pigmenting effects of whitening agents on solar lentigos (SLs), which comprise ~ 60% of hyperpigmented facial lesions of Asian subjects. Lotions with or without 6% l-ascorbate-2-phosphate trisodium salt (APS) [test lotion (TL) and placebo lotion (PL), respectively] were applied twice daily for 24 weeks in a double-bli...
Exposure of human skin to ultraviolet (UV) radiation causes significant damage to that tissue. The effects of UV on the skin mainly include acute inflammation (erythema/edema) and abnormal keratinization wherein prostaglandin E2 (produced by cyclooxygenase‐2), interleukin‐8 and transglutaminase 1 (a major regulatory factor of keratinization), play...
Supporting data for Fig 7B.
3DHEEs models were treated with (A) SSE (1 and 3 μg/mL) or (B) tiliroside (0.1 and 0.3 μg/mL) for 7 days and total protein was extracted. The protein expression levels of SPT2, GCS and GBA were determined by western blotting. Data represent the original uncropped and unadjusted blots in the Fig 7B.
(TIF)
The activation of peroxisomeproliferator-activated receptor (PPAR) α can stimulate the expression of ceramide-related enzymes, and a major component of strawberry seed extract (SSE) tiliroside enhances the expression of PPARα. We determined whether SSE and tiliroside may stimulate ceramide synthesis in the stratum corneum (SC) of the human epiderma...
TLC and HPLC chromatogram of SSE.
(DOCX)
Supporting data for data not shown Fig.
(TIF)
Supporting data for Fig 7A.
3DHEEs models were treated with (A) SSE (1 and 3 μg/mL) or (B) tiliroside (0.1 and 0.3 μg/mL) for 5 days and total protein was extracted. The protein expression levels of SPT2, GCS and GBA were determined by western blotting. Data represent the original uncropped and unadjusted blots in the Fig 7A.
(TIF)
The contents of chemical compounds and nutrition facts in SSE.
(TIF)
In the first review, we summarized the biological effects of the xanthophyll carotenoid astaxanthin (AX) to prevent UV‐induced cutaneous inflammation, abnormal keratinization, pigmentation and wrinkling in a manner independent of the depletion of reactive oxygen species. In this manuscript, we review what is known about the intracellular signaling...
We have already reported that glucosamine (GlcN) distinctly abrogates the pigmentation of human epidermal equivalents stimulated by stem cell factor + endothelin-1 (SE). In this study, we characterized the molecular mechanism involved in the anti-melanogenic effects of GlcN using normal human melanocytes (NHMs) in culture. The SE-stimulated gene (1...
We determined whether compensating ceramides in the stratum corneum (SC) may ameliorate the impaired barrier function and subsequently attenuate the enhanced skin sensitivity. Treatment for 4 weeks with the ceramide complex cream or the placebo cream significantly ameliorated the intensity of lactic acid sensations in 39 female subjects with sensit...
We recently found that treatment of normal human melanocytes (NHMs) with the antioxidant astaxanthin (AX) suppresses the stem cell factor (SCF)-stimulated protein expression levels of microphthalmia-associated transcription factor (MITF) at 1.5 h and of tyrosinase and endothelin B receptor at 96 h post-treatment. Analysis of the signaling cascade(s...
A single exposure of normal human melanocytes (NHMs) to ultraviolet B (UVB) radiation induces a distinct increase in the expression of c-KIT and endothelin B receptor (EDNRB) and up-regulates the expression of microphthalmia-associated transcription factor (MITF). In this review, we clarify the signaling mechanisms by which UVB stimulates the expre...
A screening test was used to assess more than 400 kinds of herbal extracts and related chemicals for their ability to interrupt the endothelin (EDN)1- and/or stem cell factor (SCF)-activated interacellular signaling that leads to the increased activity of tyrosinase in normal human melanocytes (NHMs). A Withania somnifera extract (WSE) and one of i...
We recently reported that the over-expression of skin fibroblast-derived neutral endopeptidase (NEP) plays a pivotal role in impairing the three-dimensional architecture of dermal elastic fibers during the biological mechanism of ultraviolet (UV)-induced skin wrinkling. In that process, a UVB-associated epithelial-mesenchymal cytokine interaction a...
In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Repetitive UVB irradiation of animal skin at suberythemal doses significantly reduces its elastic properties, resulting in the formation of wrinkles. That also elicits a marked alteration in the three-dimensional structure of...
The influence of ultraviolet B (UVB) radiation on transglutaminase 1 (TGase 1), a major factor that regulates skin keratinization, has not been sufficiently characterized especially at the gene or protein level. Thus, we determined whether UVB affects the expression of TGase 1 in human keratinocytes and clarified the intracellular stress signaling...
Melanogenesis is the physiological process by which melanin is synthesized to protect the skin from UV damage. While paracrine interactions between keratinocytes and melanocytes are crucial for regulating epidermal pigmentation, the endothelin (EDN)-endothelin B-receptor (EDNRB) interaction is one of the key linkages. In this study, we found that a...
Four maleic anhydride derivatives, tricladolides A-D (1-4), and three alkylidene succinic acid derivatives, tricladic acids A-C (5-7), were isolated from the aquatic hyphomycete Tricladium castaneicola. The structures of these compounds were determined by spectroscopic analysis, and all were found to be novel. The compounds exhibited inhibitory act...
The repetitive exposure of skin to ultraviolet B (UVB) preferentially elicits wrinkling while ultraviolet A (UVA) predominantly elicits sagging. In chronically UVB or UVA-exposed rat skin there is a similar tortuous deformation of elastic fibers together with decreased skin elasticity, whose magnitudes are greater in UVB-exposed skin than in UVA-ex...
Our previous studies strongly indicated that the up-regulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity. Fortunately, we succeeded in identifying human skin fibroblast-derived elastase as a pre...
Paracrine interactions between keratinocytes and melanocytes via cytokines play an essential role in regulating pigmentation in epidermal hyperpigmentary disorders. There is an urgent need for a human epidermal model in which melanogenic paracrine interactions between UVB-exposed keratinocytes and melanocytes can be precisely evaluated because huma...
We characterized the mechanism(s) underlying the abrogating effect of withaferin A (WFA) on the stem cell factor (SCF)-stimulated pigmentation of human epidermal equivalents (HEEs). Increased gene and protein expression levels of tyrosinase, tyrosinase-related protein1, dopachrome tautomerase, PMEL17, c-KIT and their targeted transcription factor,...
Few anti-pigmenting agents have been designed and developed according to their known hyperpigmentation mechanisms and corresponding intracellular signaling cascades. Most anti-pigmenting agents developed so far are mechanistically involved in the interruption of constitutional melanogenic mechanisms by which skin color is maintained at a normal and...
Although it has been reported that levels of hyaluronan are decreased in the dermis of aged skin, little is known about the cellular mechanism(s) underlying that hyaluronan deficiency. Since hyaluronan is produced by dermal fibroblasts and is secreted into the surrounding dermal tissues, we examined the secretion of hyaluronan by dermal fibroblasts...
Atopic dermatitis is a recurrent dermatitis which is characterized clinically by atopic dry skin and functionally by cutaneous barrier disruption even in the non-lesional skin. These abnormalities have been thought to be mainly attributable to significantly decreased levels of ceramides even in the non-lesional stratum corneum. Recently, in associa...
Atopic dermatitis is characterized by disruption of the cutaneous barrier due to reduced ceramide levels even in non-lesional dry skin. Following further acute barrier disruption by repeated tape strippings, we re-characterized the non-lesional dry skin of subjects with atopic dermatitis, which shows significantly reduced levels of barrier function...
Redox imbalances have been shown to be closely linked to a variety of altered cellular responses and profoundly affect intracellular signaling pathways, especially the PKC/MAPK pathway which is a major pathway involved in regulating melanogenesis within human melanocytes. To elucidate the effects of redox balance regulation on epidermal hyperpigmen...
We previously reported that treatment of B16 melanotic melanoma cells with reduced glutathione (GSH) converts them to amelanotic cells without any significant down-regulation of tyrosinase activity. To characterize the cellular mechanism(s) involved, we determined the intracellular distribution of melanocyte-specific proteins, especially in melanin...
We previously reported that increased expression of the endothelin (EDN)1/EDNB receptor (EDNBR) as well as the stem cell factor (SCF)/SCF receptor (c-KIT) linkages is mainly responsible for the activation of melanocytes in the epidermal hyperpigmentation of ultraviolet (UV)-B melanosis and lentigo senilis (LS). In this study, we characterized sebor...
Using B16 melanoma cells for screening, we found that a marine sponge extract has a potent anti-pigmenting effect and identified arenarol as its major active compound. In normal human melanocytes (NHMs), arenarol significantly abrogated the endothelin 1 (EDN1) stimulated expression of tyrosinase, tyrosinase-related protein 1 and dopachrome tautomer...
Background:
We previously demonstrated that the hyperpigmentation that occurs in UVB-melanosis as well as in solar lentigos is associated with the increased production of melanogenic cytokines, such as endothelin (EDN)-1 and stem cell factor (SCF), by keratinocytes in those areas of the skin.
Objective:
We developed a model for these hyperpigmen...
Although the mechanism(s) involved in the ceramide deficiency in the stratum corneum (SC) of atopic dermatitis (AD) skin is unknown, Th2 type cytokines have been reported to down-regulate ceramide levels in the epidermis. However, almost all research to date has focused on ceramide levels in the whole epidermis, not just in the SC layers alone, whi...
To elucidate the effects of redox balance regulation on cutaneous inflammation, we used the potent antioxidant astaxanthin (AX) to assess its effect on the UVB-induced secretion of PGE(2) and IL-8 in human keratinocytes and analysed its biological mechanism of action. The addition of AX (at 8 μm) to human keratinocytes even after UVB irradiation si...
We established a model for the stem cell factor (SCF)-associated stimulation of human epidermal equivalent (HEE) pigmentation. The addition of SCF (at 5 nM) gradually stimulated the visible pigmentation of HEEs over 14 days of treatment. A time course study using real-time RT-PCR and western blotting analysis demonstrated that the expression of all...
We recently reported that over-expression of skin fibroblast-derived elastase (SFE) plays a pivotal role in the mechanism of UVB-induced skin wrinkling. Since UVB penetrates only modestly to the dermis, we hypothesized that factors secreted by UVB-exposed keratinocytes in the epidermis trigger fibroblasts in the dermis to increase their expression...
We recently reported that overexpression of the elastase NEP (neutral endopeptidase) by fibroblasts plays a pivotal role in the mechanism of UVB-induced skin wrinkling by degrading dermal elastic fibres. Since UVB does not penetrate to the dermis, we hypothesized that factors secreted by UVB-exposed keratinocytes in the epidermis trigger fibroblast...
To examine factors that regulate ceramide production during keratinization of the human stratum corneum (SC), we developed a reconstructed human epidermal keratinization model in which a fresh layer of SC is newly formed within 1 week. Addition of the UDP-glucose: ceramide glucosyltransferase inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propan...
We previously demonstrated that mitogen-activated protein kinase (MAPK) signaling, including microphthalmia-associated transcription factor (MITF) and cAMP response element-binding protein (CREB) phosphorylation, is a major pathway involved in up-regulating melanogenesis within human melanocytes in several hyperpigmentary disorders such as UVB mela...
To elucidate the effects of redox balance regulation on epidermal pigmentation, we used an antioxidant-rich extract of the herb Melia toosendan (dried mature fruits) to assess its effect on endothelin-1 (EDN1)-stimulated pigmentation in human epidermal equivalents and analyzed its biological mechanism of action. Addition of the Melia toosendan extr...
Repetitive exposure of the skin to UVA radiation elicits sagging more frequently than wrinkling, which is mainly attributed to the biochemical mechanism involved in up-regulating the expression of matrix-metalloproteinase (MMP)-1 and skin fibroblast elastase (SFE), respectively. In this study, we used real-time RT-PCR, Western blotting and enzymati...
Although human skin fibroblast (HSF) elastase has been characterized as a membrane-bound metalloproteinase, little is known
about its structure, amino acid sequence, and encoding gene. As there are similarities in the molecular weights and inhibitory
profiles of HSF elastase and neprilysin (neutral endopeptidase 24.11 (NEP)), in this study we teste...
There is a general consensus that disruption of the barrier function of the stratum corneum is an essential etiologic factor for skin inflammation in patients with atopic dermatitis (AD). Since AD could be considered a barrier disease in which antigens and irritants that have penetrated (or permeated) the skin trigger and worsen the dermatitis, usi...
Repetitive exposure of the skin to UVA radiation elicits sagging more frequently than wrinkling, which is mainly attributed to its biochemical mechanism to up-regulate the expression of matrix-metalloproteinase (MMP)-1 and skin fibroblast elastase (SFE)/neutral endopeptidase (NEP), respectively.
In this study, we examined the effects of a potent an...
An imbalance of keratinocyte-derived cytok-ines and dysregulations of cytokine/receptor interactions both capable of affecting melano-cyte activity and survival has been demonstrated in vitiligo epidermis.
Melanogenic growth factors such as stem-cell factor (SCF) and endothelin (ET)-1, as well as inflammatory cytokines with anti-melanogenic propert...
KIT is an essential receptor that modulates melanocyte function and whose function is disrupted in several pigmentary disorders. However, little is known about the effects of a single UVB exposure on the expression of KIT and two important regulatory transcription factors, MITF and AP-2 alpha, in human melanocytes. We found that a single UVB exposu...
In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Repetitive irradiation of animal skin with UVB radiation at suberythemal doses significantly reduces its elastic properties, resulting in the formation of wrinkles. Repetitive UVB irradiation elicits a marked alteration in th...
Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is n...
A deficiency of ordinary ceramides in the stratum corneum is an essential etiologic factor for the dry and barrier-disrupted skin of patients with atopic dermatitis (AD). We have proposed that the mechanism underlying that deficiency involves a novel sphingolipid metabolizing enzyme, termed sphingomyelin (SM) glucosylceramide (GCer) deacylase, whic...
The hypo-pigmentation of human skin on the palms and the soles compared with other areas of the body has recently been reported to be due to mesenchymal-epithelial interactions via a fibroblast-derived factor, dickkopf 1, an inhibitor of the canonical Wnt signaling pathway. Recently, it has been reported that keratinocytes play a significant role i...
Antimicrobial peptides, such as defensin and cathelicidin, have recently been reported to play important roles in host defence and in cutaneous innate immunity. Although beta-defensin-2 has been reported to be downregulated in the skin of patients with atopic dermatitis (AD), little is known about its role in the colonization of Staphylococcus aure...
In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Cumulative irradiation with ultraviolet (UV) B at suberythemal doses significantly reduces the elastic properties of the skin, resulting in the formation of wrinkles. In in vitro studies, we identified a paracrine pathway bet...
Waardenburg syndrome (WS) is an inherited sensorineural deafness condition in humans caused by melanocyte deficiencies in the inner ear and forelock. Mutation of microphthalmia-associated transcription factor (MITF) is known to produce WS type IIA whereas mutations of either endothelin (EDN) or its receptor endothelin receptor B (EDNRB) produce WS...
IntroductionEndothelin-1/ETB Receptor Interactions between Keratinocytes and MelanocytesMembrane-bound SCF/c-KIT Interactions between Keratinocytes and MelanocytesSoluble-type SCF/c-KIT and HGF/c-MET Interactions between Fibroblasts and MelanocytesGROa/IL-8 Receptor Interactions between Keratinocytes and MelanocytesSummary and Perspectives
In vivo functions of integrins in dermis have been investigated using several types of genetically integrin deficient mice. However, there are few studies to clarify actual in vivo functions of integrins in the dermis using normal type animals.
We investigated the actual in vivo functions of integrins in maintaining structural and mechanical proper...
Previously, we have demonstrated that fibroblast-derived elastase plays an essential role in the increased three-dimensional tortuosity of elastic fibers, contributing to the loss of skin elasticity in UV-B-exposed skin. This decrease in skin elasticity is closely associated with the formation of wrinkles induced by UV exposure.
To further clarify...
The 4th Georg Rajka International Symposium on Atopic Dermatitis presented a comprehensive view of our current understanding and management of atopic dermatitis (AD). These proceedings highlight contributions related to the history of AD doctrines; genetic and epigenetic background; epidemiology; maturation of the immune system; infection and innat...
Hair lipid images, as visualized by argon sputter etching-scanning electron microscopy (ASE-SEM), reveal convex structures with a stitch pattern (SP) at the cell membrane complex (CMC) in the transverse hair plane. Based on interindividual variation, different features of the convex SP were classified into Types 0 to 4 with the corresponding scores...
Hair lipids localized at the cell membrane complex (CMC) play a part in chemical diffusion, cell cohesion, and mechanical strength. There is no method currently available to visualize hair lipids at the CMC. We found that scanning electron microscopy (SEM) of a transversely polished hair plane followed by argon sputter etching (ASE) provides a spec...
As one of the major skin fatty acids, cis-6-hexadecenoic acid (C16:1Delta6) exhibits a specific antibacterial activity and might play a specific role in the defense mechanism against Staphylococcus aureus, in healthy subjects whereas S. aureus frequently colonizes the skin of patients with atopic dermatitis (AD).
Fatty acid composition of sebum at...
A systematic method for the sensitive, precise and accurate determination of hair lipids, including trace amounts of intrinsic endogenous cholesterol (CH), ceramide/N-palmitoyl-DL-dihydrosphingosine (CER/PDS), cholesterol sulfate (CS) and chemically bound 18-methyl eicosanoic acid (18-MEA), has been developed in combination with TLC/FID (flame ioni...
