Shiseido Research Center

Tsuzuki ku, Japan

Shiseido Research Center

Tsuzuki ku, Japan
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Ezure T.,Shiseido Research Center | Amano S.,Shiseido Research Center
Experimental Dermatology | Year: 2010

Please cite this paper as: Increased subcutaneous adipose tissue impairs dermal function in diet-induced obese mice. Experimental Dermatology 2010; 19: 878-882. Abstract: Increment of subcutaneous adipose tissue is a risk factor for facial morphological changes, such as sagging, which may be at least partly because of the increased weight burden of accumulated fat. However, it is not clear how the increase of subcutaneous adipose tissue affects dermal structure and function. We examined this issue in HR-1 hairless mice given a high-fat diet (HFD). After having been fed with HFD for 12weeks, the mice became obese and the subcutaneous adipose tissue layer was significantly thickened, while the dermal layer became significantly thinner than that of control mice fed normal diet. However, the thickness of the dermal layer was not changed in the ear pinna, which lacks a subcutaneous adipose layer, suggesting that increase of subcutaneous adipose tissue may induce dermal changes. The number of dermal fibroblasts in the dermis was significantly reduced in obese mice, although there was no change in gene expression levels of extracellular matrix components, including collagen, hyaluronic acid synthase, fibulin5, fibrillin-1, laminin β1, matrix metalloproteinases and tissue inhibitor of metalloproteinases. Dermal elasticity was significantly decreased in obese hairless mice. These results suggest that subcutaneous adipose cells in obese mice may reduce the proliferation of dermal fibroblasts and induce a decrease of dermal thickness and elasticity. Therefore, the increment of the subcutaneous adipose layer in obese subjects may induce impairment of dermal biomechanical characteristics and promote the appearance of sagging. © 2009 John Wiley & Sons A/S.


Ezure T.,Shiseido Research Center | Amano S.,Shiseido Research Center
Journal of Investigative Dermatology | Year: 2011

Subcutaneous adipose tissue lies just beneath the dermal layer, but the interaction between the two types of tissue remains obscure. Recently, we reported that obesity is associated with decreased dermal elasticity. To investigate the mechanism of the adipose tissue/dermal interaction, fibroblasts were cocultured with small or enlarged adipocytes, using a membrane insert to prevent direct contact. Enlarged adipocytes reduced 3T3-L1 fibroblast proliferation and gene expression of collagen (I)-α1 (col (I)-α1) and elastin while increasing gene expression of matrix metalloproteinase 13 (MMP13). In contrast, small adipocytes had no such effects. These results indicate that factors secreted by enlarged adipocytes influence dermal condition. As enlarged adipocytes are known to release free fatty acids (FFAs), the effects of these acids on 3T3-L1 fibroblasts were examined. Palmitic acid decreased fibroblast proliferation, reduced gene expressions of col (I)-α1 and elastin, and increased MMP13. Similar effects were observed in human dermal fibroblasts. The influence of palmitic acid on fibroblasts was inhibited by eicosapentaenoic acid (EPA), an inhibitor of Toll-like receptors (TLRs). Furthermore, EPA inhibited the effects of enlarged adipocytes on fibroblasts in the coculture system. These data indicate that enlarged adipocytes negatively control the function of dermal fibroblasts through the activation of TLRs by secreted FFAs. © 2011 The Society for Investigative Dermatology.


Denda M.,Shiseido Research Center | Tsutsumi M.,Shiseido Research Center
Advances in Experimental Medicine and Biology | Year: 2011

Epidermal keratinocytes are the epithelial cells of mammalian skin. At the basal layer of the epidermis, these cells proliferate strongly, and as they move towards the skin surface, differentiation proceeds. At the uppermost layer of the epidermis, keratinocytes undergo apoptosis and die, forming a thin, water-impermeable layer called the stratum corneum. Peripheral blood vessels do not reach the epidermis, but peripheral nerve fibers do penetrate into it. Until recently, it was considered that the main role of epidermal keratinocytes was to construct and maintain the water-impermeable barrier function. However, since the functional existence of TRPV1, which is activated by heat and low pH, in epidermal keratinocytes was identified, our understanding of the role of keratinocytes has changed enormously. It has been found that many TRP channels are expressed in epidermal keratinocytes, and play important roles in differentiation, proliferation and barrier homeostasis. Moreover, because TRP channels expressed in keratinocytes have the ability to sense a variety of environmental factors, such as temperature, mechanical stress, osmotic stress and chemical stimuli, epidermal keratinocytes might form a key part of the sensory system of the skin. The present review deals with the potential roles of TRP channels expressed in epidermal keratinocytes and focuses on the concept of the epidermis as an active interface between the body and the environment. © 2011 Springer Science+Business Media B.V.


Arimoto H.,Japan National Institute of Advanced Industrial Science and Technology | Egawa M.,Shiseido Research Center
Skin Research and Technology | Year: 2015

Background/purpose: We investigate the measurement sensitivity for the water content distribution in Near-infrared (NIR) imaging ranging up to 2 μm. Methods: To evaluate the sensitivity, our attention is focused to the light penetration depth in the skin tissue because the thickness of a layer where the water content can be varied is very thin and deep light penetration decreases the signal variation. The light penetration depths in the wavelengths of 1300, 1450, and 1920 nm are calculated theoretically based on the Monte Carlo light transport simulation. Results: It is clarified that the wavelength of 1920 nm gives the smallest penetration depth. A NIR imaging experiment is demonstrated to verify the difference of imaging sensitivity. The experiment result shows that the NIR image taken at 1920 nm gives the most sensitive measurement of the water content distribution in skin. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Egawa M.,Shiseido Research Center | Sato Y.,Shiseido Research Center
Skin Research and Technology | Year: 2015

Background/purpose: As urea is one of the natural moisturizing factor (NMF) components in the stratum corneum, it has been used in topical products to improve skin conditions. However, the penetration behavior of urea in the skin after application of urea-containing cream has not been determined as there has been no technique with which to measure the urea content in the skin in vivo non-invasively. We therefore applied Raman spectroscopy to evaluate the depth profile of urea content in the skin. We investigated changes in depth profiles of two forms of urea to evaluate the penetration behavior of urea after application of urea-containing cream. Methods: Commercially available moisturizing creams F and R in quantities of 2.2-mg/cm2 and containing 20% (w/w) urea were applied to volar forearm skin of six Japanese subjects. Raman spectra of the skin were measured at 2-μm intervals from the skin surface toward the interior using a confocal Raman spectrometer (model 3510 SCA) before and 15, 60, and 120 min after the application of the creams. The amounts of the two forms of urea, urea in water solution and urea in a solid state, were calculated by adding the spectra of solid urea and the cream base to a previously reported algorithm including the spectrum of urea in water solution. Results: The characteristic band of urea in water solution was observed at approximately 1004/cm and that of the solid state at approximately 1010/cm in the Raman spectra of the skin after application of either cream. There was more urea in water solution form in the area where cream F was applied than in the area where cream R was applied. There was more urea in a solid state in the area where cream R was applied than in the area where cream F was applied at all depths and measurement times. In particular, there was significantly more urea in a solid state below a depth of 2 μm in the area where cream R was applied than in the area where cream F was applied 15 min after application. Conclusion: The present study demonstrated that we can measure both urea forms in the skin after the application of urea-containing creams. The proposed technique would be useful in the evaluation of characteristics of the penetration behavior of urea in the skin after the application of various urea-containing moisturizers. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Inomata S.,Shiseido Research Center
Journal of Oleo Science | Year: 2014

The Japanese Pharmaceutical Affairs Law distinguishes cosmetics from quasi-drugs, and specifies that they must have a mild effect on the human body and must be safe to use over the long term. Therefore, the safety of cosmetics needs to be thoroughly evaluated and confirmed, taking into account the type of cosmetic, application method, conditions of use and so on. Post-marketing surveys of customers' complaints and case reports of adverse effects are important to monitor and confirm the safety of products. Although manufacturing and marketing of cosmetics are becoming more globalized, the regulations relevant to cosmetics safety still vary from country to country. Thus, compliance with different regulations in various markets is a major issue for producers. In particular, further development of alternatives to animal testing remains an urgent global issue. ©2014 by Japan Oil Chemists' Society.


Sun-exposed skin is characterized by superficial changes such as wrinkles, sagging and pigmentary changes, and also many internal changes in the structure and function of epidermis, basement membrane (BM) and dermis. These changes (so-called photoageing) are predominantly induced by the ultraviolet (UV) component of sunlight. Epidermis of UV-irradiated skin produced several enzymes such as matrix metalloproteinases (MMPs), urinary plasminogen activator (uPA)/plasmin and heparanase, which degrade dermal collagen fibres and elastic fibres in the dermis, and components of epidermal BM. The BM at the dermal–epidermal junction (DEJ) controls dermal–epidermal signalling and plays an important role in the maintenance of a healthy epidermis and dermis. BM is repetitively damaged in sun-exposed skin compared with unexposed skin, leading to epidermal and dermal deterioration and accelerated skin ageing. UV exposure also induces an increase in vascular endothelial growth factor (VEGF), an angiogenic factor, while thrombospondin-1 (TSP-1), an anti-angiogenic factor, is decreased; these changes induce angiogenesis in papillary dermis with increased migration of elastase-positive leucocytes, leading to dermal elastic fibre damage. Elastic fibres, such as oxytalan fibres in papillary dermis, are associated with not only skin resilience, but also skin surface texture, and elastic fibre formation by fibroblasts is facilitated by increased expression of fibulin-5. Thus, induction of fibulin-5 expression is a damage-repair mechanism, and fibulin-5 is an early marker of photoaged skin. UV-induced skin damage is cumulative and leads to premature ageing of skin. However, appropriate daily skincare may ameliorate photoageing by inhibiting processes causing damage and enhancing repair processes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


Ezure T.,Shiseido Research Center | Amano S.,Shiseido Research Center
Skin Research and Technology | Year: 2010

Background: Most studies on wrinkle formation have focused on changes in the dermal condition that promote the fixation of transiently formed wrinkles. Little is known about the age-dependent changes in transient wrinkle formation in response to altered facial expression or the mechanism leading to fixed wrinkle formation. Objective: To clarify the mechanism of wrinkle formation at the forehead, we investigated the factors that influence the severity of transient wrinkling and the relationship of transient with fixed wrinkles, using a newly established method to evaluate transient wrinkle formation. Methods: Transient wrinkles were generated by requesting subjects to gaze in an upward direction. Foreheads of the subjects with or without an upward gaze at a fixed angle were photographed and the severity of wrinkles at the forehead was graded from 0 to 5 in 50 healthy Japanese female volunteers in their 20s, 40s, or 60s. Skin elasticity was measured using a Cutometer®. Frontalis muscle activity and ptosis of the upper eyelid were estimated by measuring movement of the eyebrow during upward gazing and the position of the upper eyelid of the open eye, respectively. Results: Wrinkles formed transiently at the forehead by upward gazing were highly reproducible in each subject. Their severity increased with aging and was highly correlated to that of fixed wrinkles (R=0.81, P<0.001). Therefore, this method appears to be suitable for studying the mechanism of transient wrinkle formation and the relationship between transient and fixed wrinkles at the forehead. The severity of transient wrinkles was correlated with elevation of the eyebrow during upward gazing (R=0.69, P<0.001), but not with dermal elasticity. This suggests that transient wrinkles are induced by increased frontalis muscle activity during upward gazing. Frontalis muscle activation was negatively correlated with upper eyelid position (R=-0.37, P<0.05), which descended with aging, meaning ptosis of the upper eyelid, and negatively correlated with the severity of transient wrinkles induced by upward gazing (R=-0.43, P<0.05). Furthermore, the upper eyelid position was also negatively correlated with the severity of fixed wrinkles (R=-0.44, P<0.05). Conclusion: These results suggest that ptosis of the upper eyelid is associated with increased activation of the frontalis muscle during upward gazing and increased severity of transient and fixed wrinkling at the forehead. © 2010 John Wiley & Sons A/S.


Ezure T.,Shiseido Research Center | Amano S.,Shiseido Research Center
Skin Research and Technology | Year: 2010

Background: Subcutaneous adipose tissue lies just beneath the dermal layer, but the interaction between the two is not well understood. Recently, we showed that the subcutaneous adipose layer affects dermal properties in an obese rodent model. Objective: To explore the influence of the subcutaneous adipose layer on dermal properties and morphology in humans. Methods: Subcutaneous adipose mass was measured by ultrasound using a Prosound alpha 5®, dermal elasticity was measured using an in vivo suction skin elasticity meter (Cutometer MPA 580®), and sagging severity were evaluated morphologically using photograph-based grading criteria at the lower cheek in 70 Japanese female volunteers (age; 31-59, BMI; 17.1-36.2). The correlations among the results were examined. Results: Thickness of the subcutaneous adipose layer was significantly and negatively correlated with dermal elasticity parameters, i.e., elastic deformation, elastic deformation recovery, extensibility, total deformation recovery, ratio of viscoelasticity to elastic distention and overall elasticity, including creep and creep recovery. Furthermore, we investigated their influence on facial morphology, such as sagging. The subcutaneous adipose mass was significantly and positively correlated with sagging severity at the lower cheek (R=0.442, P<0.001), and there was a significant negative correlation between dermal elasticity and sagging severity (R=-0.358, P<0.01). Conclusion: These results indicate that increment of subcutaneous adipose mass impairs dermal elasticity, which in turn exacerbates sagging severity. © 2010 John Wiley & Sons A/S.


Sawane M.,Shiseido Research Center | Kajiya K.,Shiseido Research Center
Experimental Dermatology | Year: 2012

Ultraviolet light in the 290- to 320-nm wavelength range (UVB) induces angiogenesis and lymphatic dysfunction in skin. This review deals with UVB-induced alterations to the blood and lymphatic systems in skin and the molecular mechanisms involved. We also discuss potential strategies to block photoageing of skin by inhibiting angiogenesis and/or promoting lymphatic vascular function. © 2012 John Wiley & Sons A/S.

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