Kao Biological Science Laboratories

Haga, Japan

Kao Biological Science Laboratories

Haga, Japan

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Kawashima M.,Tokyo Women's Medical University | Yokose U.,Kao Biological Science Laboratories | Hachiya A.,Kao Biological Science Laboratories | Fujimura T.,Kao Biological Science Laboratories | And 6 more authors.
European Journal of Dermatology | Year: 2013

Wrinkles, one of the characteristics of chronic sun-damaged and/or aged skin, are associated with psychological distress. Apart from the deterioration of collagen and elastic fibers in the dermis, which induces the loss of skin elasticity, it has been recently proposed that decreased flexibility or elasticity of the stratum corneum (SC) is also correlated with wrinkle formation. The elasticity of the SC has been shown to be regulated, at least in part, by the amounts and types of amino acids. To evaluate the ability of our newly developed amino acid-derivative (1-carbamimidoyl- L-proline; CLP), which recovers the elastic properties of the SC ex vivo, to improve wrinkles, a clinical test was performed with 126 Japanese female subjects aged 32-50 years who had crow's feet lines on their faces. Three eligible dermatologists evaluated the study according to authorized grades by the Japanese Cosmetic Science Society and scored the subjects who were much improved or improved as 29.7% and 57.8% of all CLP-treated subjects at 4 and 8 weeks, respectively. In contrast, only 1.5% and 8.1% of subjects improved with the placebo lotion at 4 and 8 weeks, respectively. These results suggest a significant efficacy of CLP to improve wrinkles. In parallel with the dermatologists' assessments, skin surface roughness in the CLP-treated group was significantly reduced after treatment with CLP for 4 and 8 weeks compared to the placebo-treated group. The sum of these data suggests that CLP is a promising and useful ingredient for the improvement of wrinkles through its ability to enhance the elasticity of the SC.


Morisaki N.,Kao Biological Science Laboratories | Moriwaki S.,Kao Biological Science Laboratories | Sugiyama-Nakagiri Y.,Kao Biological Science Laboratories | Haketa K.,Kao Biological Science Laboratories | And 2 more authors.
Journal of Biological Chemistry | Year: 2010

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 tested the hypothesis that they are identical using immunoprecipitation and transfection methods. An immunoprecipitation study demonstrated that HSF elastase activity co-immunoprecipitated with anti-NEP in lysates of cultured HSF. Transfection of an NEP cDNA expression vector into COS-1 cells elicited the expression of HSF elastase and NEP activities in the transfected cells. These findings strongly suggest that HSF elastase is identical to NEP, which functions mainly in neuron-associated cells to degrade neuropeptides. Analysis of the expression pattern of NEP revealed that its expression was remarkably up-regulated at the gene, protein, and enzymatic activity levels during the replicative senescence of cultured HSF. Further, the activity of NEP was markedly enhanced in a pattern similar to elastase activity during the intrinsic aging of mouse skin, in UVA-exposed HSF as well as in HSF treated with conditioned medium from UVB-exposed human keratinocytes. Analysis of the cytokine profile for the stimulation of NEP and HSF elastase activities in HSF demonstrated that among the 11 cytokines tested, IL-1α, IL-1β, IL-6, IL-8, and GM-CSF had the potential to significantly stimulate both activities similarly, again supporting the identity of HSF elastase and NEP. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Yokose U.,Kao Biological Science Laboratories | Hachiya A.,Kao Biological Science Laboratories | Sriwiriyanont P.,University of Cincinnati | Fujimura T.,Kao Biological Science Laboratories | And 7 more authors.
Journal of Investigative Dermatology | Year: 2012

UVB exposure is well known to induce skin photodamage and photoaging that correlates with qualitative and quantitative deterioration of the dermal extracellular matrix (ECM) because of the upregulation of matrix metalloproteinases (MMPs). Although inhibitory effects of tissue inhibitor of metalloproteinases (TIMPs) on most MMPs have been reported, the protective role of TIMP-1 against photodamage is poorly understood. To address this, TIMP-1 function was augmented or abolished in a human skin xenograft photodamage model after the confirmation of significantly diminished TIMP-1 expression both in photoaged and intrinsically aged skins. During a chronic UVB exposure regimen, pre-treatment with a lentiviral vector overexpressing TIMP-1 or concomitant administration of an anti-TIMP-1-neutralizing antibody (NAB) led to photoprotection or more severe photodamage, respectively. Overexpression of TIMP-1 resulted in significant inhibition of UVB-induced ECM degradation, as well as suppression of decreased skin elasticity and roughness, whereas the NABmediated inhibition of TIMP-1 had opposite effects. Furthermore, UVB-induced production of the proinflammatory cytokine, tumor necrosis factor a, was inhibited by TIMP-1 treatment of human keratinocytes. Taken together, these data shed light on the important role of TIMP-1 in protection and recovery from cutaneous photodamage because of its suppression of ECM degradation and inflammation. © 2012 The Society for Investigative Dermatology.


Murase D.,Kao Biological Science Laboratories | Hachiya A.,Kao Biological Science Laboratories | Takano K.,Kao Biological Science Laboratories | Hicks R.,Kao Biological Science Laboratories | And 5 more authors.
Journal of Investigative Dermatology | Year: 2013

Melanin in the epidermis determines the wide variation in skin color associated with ethnic skin diversity. Ethnic differences exist regarding melanosome loss in keratinocytes, but the mechanisms underlying these differences, and their contribution to the regulation of skin color, remain unclear. Here, we explored the involvement of autophagy in determining skin color by regulating melanosome degradation in keratinocytes. Keratinocytes derived from Caucasian skin exhibit higher autophagic activity than those derived from African American (AA) skin. Furthermore, along with the higher autophagy activity in Caucasian skin-derived keratinocytes compared with AA skin-derived keratinocytes, Caucasian skin-derived keratinocytes were more sensitive to melanosome treatment as shown by their enhanced autophagic activity, which may reflect the substantial mechanisms in the human epidermis owing to the limitations of the models. Melanosome accumulation in keratinocytes was accelerated by treatment with lysosomal inhibitors or with small interfering RNAs specific for autophagy-related proteins, which are essential for autophagy. Furthermore, consistent with the alterations in skin appearance, the melanin levels in human skin cultured ex vivo and in human skin substitutes in vitro were substantially diminished by activators of autophagy and enhanced by the inhibitors. Taken together, our data reveal that autophagy has a pivotal role in skin color determination by regulating melanosome degradation in keratinocytes, and thereby contributes to the ethnic diversity of skin color. © 2013 The Society for Investigative Dermatology.


Sriwiriyanont P.,University of Cincinnati | Sriwiriyanont P.,Cincinnati Childrens Hospital Medical Center | Hachiya A.,Kao Biological Science Laboratories | Pickens W.L.,Cincinnati Childrens Hospital Medical Center | And 7 more authors.
Journal of Investigative Dermatology | Year: 2011

The hair follicle has a unique dynamic property to cyclically regenerate throughout life. Despite significant progress in hair structure and hair shape determination using animal models, the mechanisms controlling the architecture and the shape of the human hair remain largely unexplored. In this study, comparison of the genetic expression of several human genes, especially those involved in growth, development, and differentiation, between Caucasian curly hair and naturally straight hair was performed. Thereafter, analyses using human recombinant and lentiviral vector technologies were conducted to further dissect and elucidate a molecular mechanism that regulates hair growth and development, particularly in controlling the shape of the hair shaft. Overexpression of IGF-binding protein 5 (IGFBP-5) in the human hair xenografts obtained from straight- and curly-haired individuals was found to result in the decreased expression of several extracellular matrix proteins and disassembly of adhesional junctions, resulting in twisted hair shafts as well as an unusual deposition of hair cuticle that may be derived from the disturbance of normal proliferation and differentiation. This study provides evidence that IGFBP-5 has an effect on human hair shape, and that lentiviral transduction regimen can be used for functional analysis of genes involved in human hair morphogenesis. © 2011 The Society for Investigative Dermatology.


PubMed | Kao Biological Science Laboratories
Type: Journal Article | Journal: The Journal of investigative dermatology | Year: 2012

UVB exposure is well known to induce skin photodamage and photoaging that correlates with qualitative and quantitative deterioration of the dermal extracellular matrix (ECM) because of the upregulation of matrix metalloproteinases (MMPs). Although inhibitory effects of tissue inhibitor of metalloproteinases (TIMPs) on most MMPs have been reported, the protective role of TIMP-1 against photodamage is poorly understood. To address this, TIMP-1 function was augmented or abolished in a human skin xenograft photodamage model after the confirmation of significantly diminished TIMP-1 expression both in photoaged and intrinsically aged skins. During a chronic UVB exposure regimen, pre-treatment with a lentiviral vector overexpressing TIMP-1 or concomitant administration of an anti-TIMP-1-neutralizing antibody (NAB) led to photoprotection or more severe photodamage, respectively. Overexpression of TIMP-1 resulted in significant inhibition of UVB-induced ECM degradation, as well as suppression of decreased skin elasticity and roughness, whereas the NAB-mediated inhibition of TIMP-1 had opposite effects. Furthermore, UVB-induced production of the pro-inflammatory cytokine, tumor necrosis factor , was inhibited by TIMP-1 treatment of human keratinocytes. Taken together, these data shed light on the important role of TIMP-1 in protection and recovery from cutaneous photodamage because of its suppression of ECM degradation and inflammation.


PubMed | Kao Biological Science Laboratories
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2010

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 tested the hypothesis that they are identical using immunoprecipitation and transfection methods. An immunoprecipitation study demonstrated that HSF elastase activity co-immunoprecipitated with anti-NEP in lysates of cultured HSF. Transfection of an NEP cDNA expression vector into COS-1 cells elicited the expression of HSF elastase and NEP activities in the transfected cells. These findings strongly suggest that HSF elastase is identical to NEP, which functions mainly in neuron-associated cells to degrade neuropeptides. Analysis of the expression pattern of NEP revealed that its expression was remarkably up-regulated at the gene, protein, and enzymatic activity levels during the replicative senescence of cultured HSF. Further, the activity of NEP was markedly enhanced in a pattern similar to elastase activity during the intrinsic aging of mouse skin, in UVA-exposed HSF as well as in HSF treated with conditioned medium from UVB-exposed human keratinocytes. Analysis of the cytokine profile for the stimulation of NEP and HSF elastase activities in HSF demonstrated that among the 11 cytokines tested, IL-1, IL-1, IL-6, IL-8, and GM-CSF had the potential to significantly stimulate both activities similarly, again supporting the identity of HSF elastase and NEP.

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