• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.12-25
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• 2003

L-camitine ($\beta$ -hydroxy-${\gamma}$ -trimethyl-ammoniumbutyric acid) is a small water-soluble molecule important in mammalian fat metabolism. It is essential for the normal oxidation of fatty acids by the mitochondria, and is involved in the trans-esterification and excretion of acyl-CoA esters. In this paper, to investigate the relationship between aging and L-camitine, we investigated the effects of in vitro MMP inhibition and activity and expression of UVA-induced MMP 1 in human skin fibroblasts. Fluorometric assays of the proteolytic activities of MMP-l were performed using fluorescent collagen substrates. ELISA (enzyme linked immuno sorbent assay), gelatin-substrate zymography, and RT-PCR ELISA techniques were used for the effects of L-camitine on MMP expression and activity, MMP mRNA expression in UVA irradiated fibroblast. L-camitine inhibited the activities of MMP-l in a dose-dependent manner and the $IC_{50}$/ values calculated from semi-log plots were 2.45mM, and L-carnitine showed strong inhibition on MMP-2 (gelatinase) activity in UVA irradiated fibroblast by zymography. Also, UVA induced MMP expression was reduced 40% by treated with L-carnitine, and MMP-l mRNA expression was reduced dose-dependent manner. Therefore L-carnitine was able to significantly inhibition the MMP activity, regulation of MMP expression in protein and mRNA level. All these results suggest that L-carnitine may be useful as new anti-aging cofactor for protection against UVA induced MMP expression and activity.

• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.249-260
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• 2024

New supplements with preventive effects against skin photodamage are receiving increasing attention. This study evaluated the anti-photoaging effects of salmon nasal cartilage proteoglycan (SPG), acting as a functional material for skin health. We administered SPG to in vitro and in vivo models exposed to ultraviolet B (UVB) radiation and assessed its moisturizing and anti-wrinkle effects on dorsal mouse skin and keratinocytes and dermal fibroblasts cell lines. These results showed that SPG restored the levels of filaggrin, involucrin, and AQP3 in the epidermis of UVB-irradiated dorsal skin and keratinocytes, thereby enhancing the keratinization process and water flow. Additionally, SPG treatment increased the levels of hyaluronan and skin ceramide, the major components of intercellular lipids in the epidermis. Furthermore, SPG treatment significantly increased the levels of collagen and procollagen type 1 by down-regulating matrix metalloproteinase 1, which play a crucial role in skin fibroblasts, in both in vitro and in vivo models. In addition, SPG strongly inhibited mitogen-activated protein kinase (MAPKs) signaling, the including extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38. These findings suggest that dietary SPG may be an attractive functional food for preventing UVB-induced photoaging. And this SPG product may provide its best benefit when treating several signs of skin photoaging.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.123-132
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• 2000

$TGF-{\beta}_1$ is a potent chemotactic factor for inflammatory cells and fibroblasts. It also stimulates the celluar source and components of extracellular matrix and the production of proteinase inhibitors. Collectively, these biologic activities lead to the accumulation and stabilization of the nascent matrix, which is vital to infection control. The objective of this study is to investigate production of $TGF-{\beta}$ in vitro fibroblast culture in the presence of Staphylococcus enterotoxin B(SEB) and/or lipopolysaccharide(LPS) and to elucidate the role of $TGF-{\beta}_1$ which may be responsible for infection control. The fibroblasts were originated from gingiva and facial dermis in 26 year-old male patient. In the presence of LPS($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$), SEB($0.01{\mu}g$, $0.l{\mu}g$, $1.0{\mu}g$) respectively, $cells(5{\times}10^3ml)$ were cultivated in vitro. At 1, 3, and 5 days after incubation, cells were counted. Also, $cells(2.5{\times}10^5ml)$ were cultivated in EMEM with LPS(0.01, 0.1 and $1.0{\mu}g$), SEB(0.01, 0.1 and $1.0{\mu}g$) respectively and $LPS(0.1{\mu}g)$ and $SEB(0.1{\mu}g)$ in combination for 24, 48, and 72 hours respectively. Culture supernatants were harvested at 1, 2, and 3 days after incubation period and triplicate culture supernatants were pooled and $TGF-{\beta}_1$ was assayed in duplicate. The results were as follows. 1. In gingival fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell Proliferation occurred very significantly since 3 days after incubation, compared with the control and the production of $TGF-{\beta}_1$ occurred very significantly at 1 day after incubation, compared with the control. 2. In facial dermal fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation occurred very significantly at 1 day after incubation, compared with the control. In SEB exposure, the production of $TGF-{\beta}_1$ was decreased very significantly at 1 day after incubation, compared with the control. However, in LPS, SEB and LPS exposure, the production of $TGF-{\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. In conclusion, the concentration of bacterial toxins and the incubation period correlated with cell proliferation and production of $TGF-{\beta}_1$ very significantly. The gingival and facial dermal fibroblasts have different phenotype each other The orchestrated understanding of fibroblast proliferation and $TGF-{\beta}_1$ production play an important part in host defense against the bacterial Infection and may prevent tissue necrosis such as necrotizing fasciitis and life-threatening syndrome such as multiple organ failure.

• Journal of Food Hygiene and Safety
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• v.32 no.3
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• pp.243-248
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• 2017

Intracellular and extracellular oxidative stress initiated by reactive oxygen species (ROS) causes skin aging, which is characterized by wrinkles and atypical pigmentation. Use of antioxidant is an effective approach to prevent symptoms related to ROS-induced aging of the skin. Therefore, the antioxidant and anti-aging effect of Castanea crenata Siebold & Zucc. extracts (LCE) was investigated in this study. The LCE markedly reduced the hydrogen peroxide-induced cell damage, intracellular ROS, and oxidative stress-induced senescence in human dermal fibroblasts (HDFs). These results indicate that LCE might have beneficial effects on oxidative stress-induced damage and thus reduce skin aging.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.220-229
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• 2008

Purpose: The present study was aimed to examine the effect of acellular dermal matrix ($AlloDerm^{(R)}$) grafted to the experimental tissue defect on tissue regeneration. Materials and Methods: Male albino rabbits were used. Soft tissue defects were prepared in the external abdominal oblique muscle. The animals were then divided into 3 groups by the graft material used: no graft, autogenous dermis graft, and $AlloDerm^{(R)}$ graft. The healing sites were histologically examined at weeks 4 and 8 after the graft. In another series, critical sized defects with 8-mm diameter were prepared in the right and left iliac bones. The animals were then divided into 5 groups: no graft, grafted with autogenous iliac bone, $AlloDerm^{(R)}$ graft, $AlloDerm^{(R)}$ graft impregnated with rhBMP-2, and $AlloDerm^{(R)}$ graft with rhTGF-${\beta}1$. The healing sites of bone defect were investigated with radiologic densitometry and histological evaluation at weeks 4 and 8 after the graft. Results: In the soft tissue defect, normal healing was seen in the group of no graft. Inflammatory cells and foreign body reactions were observed in the group of autogenous dermis graft, and the migration of fibroblasts and the formation of vessels into the collagen fibers were observed in the group of $AlloDerm^{(R)}$ graft. In the bone defect, the site of bone defect was healed by fibrous tissues in the group of no graft. The marked radiopacity and good regeneration were seen in the group of autogenous bone graft. There remained the traces of $AlloDerm^{(R)}$ with no satisfactory results in the group of $AlloDerm^{(R)}$ graft. In the groups of the $AlloDerm^{(R)}$ graft with rhBMP-2 or rhTGF-${\beta}1$, there were numerous osteoblasts in the boundary of the adjacent bone which was closely approximated to the $AlloDerm^{(R)}$ with regeneration features. However, the fibrous capsule also remained as in the group of $AlloDerm^{(R)}$ graft, which separated the $AlloDerm^{(R)}$ and the adjacent bone. Conclusions: These results suggest that $AlloDerm^{(R)}$ can be useful to substitute the autogenous dermis in the soft tissue defect. However, it may not be useful as a bone graft material or a carrier, since the bone defect was not completely healed by the bony tissue, regardless of the presence of osteogenic factors like rhBMP-2 or rhTGF-${\beta}1$.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.354-360
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• 2020

The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)-Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)-glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.2
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• pp.163-171
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• 2016

Steroid hormone, glucocorticoid (GC) has strong anti-inflammatory effects by binding to glucocorticoid receptor (GR) inhibiting the expression of inflammatory genes. Therefore, agents that activate the GR have been used for the treatment of dermatitis. However, the agents have side effects such as skin barrier dysfunction and dermal atrophy, inducing skin damage as well as skin aging. It has been reported that GC is activated by 11 beta-hydroxysteroid dehydrogenase type 1 ($11{\beta}$-HSD1) to increase the activity of the GR. This study aimed to identify natural materials that can effectively inhibit dexamethasone. We found that alpinetin isolated from Alpinia katsumadai extract has a significant effect on this. Alpinetin not only inhibited $11{\beta}$-HSD1 expression, but also suppressed the increase of phosphorylated GR and cortisol concentration. Alpinetin also recovered collagen expression in dexamethasone-treated dermal fibroblasts, and the reduction of dermal thickness in dexamethasnone-treated 3D skin model. These results suggest that alpinetin prevents skin aging induced by the increase of $11{\beta}$-HSD1 expression.

• Journal of Periodontal and Implant Science
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• v.32 no.1
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• pp.129-142
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• 2002

Epithelial-mesenchymal interaction plays a important role in cell growth and differentiation. This interaction is already well known to have an importance during the organ development as well as cell growth and differentiation. However, in vitro experimental model is not well developed to reproduce in vivo cellular microenvironment which provide a epithelial-mesenchymal interaction. Because conventional monolayer culture lacks epithelial-mensenchymal interaction, cultivated cells have an morphologic, biochemical, and functional characteristics differ from in vivo tissue. Moreover, it's condition is not able to induce cellular differention due to submerged culture condition. Therefore, the aims of this study were to develop and evaualte the in vitro experimental model that maintains epithelial-mesenchymal interaction by organotypic raft culture, and to characterize biologic properties of three-dimensionally reconstituted oral keratinocytes by histological and immunohistochemical analysis. The results were as follow; 1. Gingival keratinocytes reconstituted by three-dimensional organotypic culture revealed similar morphologic characteristics to biopsied patient specimen showing stratification, hyperkeratinosis, matutation of epithelial architecture. 2. Connective tissue structure was matured, and there is no difference during stratification period of epithelial 3-dimensional culture. 3. The longer of air-exposure culture on three-dimensionally reconstituted cells, the more epithelial maturation, increased epithelial thickness and surface keratinization 4. In reconstitued mucosa, the whole epidermis was positively stained by anti-involucrin antibody, and there is no difference according to air-exposured culture period. 5. The Hsp was expressed in the epithelial layer of three-dimensionally cultured cells, especially basal layer of epidermis. The change of Hsp expression was not significant by culture stratification. 6. Connexin 43, marker of cell-cell communication was revealed mild immunodeposition in reconstitued epithelium, and there is no significant expression change during stratification. These results suggest that three-dimensional oragnotypic co-culture of normal gingival keratinocytes with dermal equivalent consisting type I collagen and gingival fibroblasts results in similar morphologic and immunohistochemical characteristics to in vivo patient specimens. And this culture system seems to provide adequate micro-environment for in vitro tissue reconstitution. Therefore, further study will be focused to study of in vitro gingivitis model, development of novel perioodntal disease therapeutics and epithelial-mensenchymal interaction.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.31 no.4 s.54
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• pp.323-327
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• 2005

Although many studies have been performed to elucidate the molecular consequence of ultraviolet irradiation on an aging, little is known about the effect of natural products. Matrix metalloproteinases (MMPs) we known to play an important role in (a) photoaging. Hete we investigated the effect of $1,2,4,6-tetra-O-galloyl-{\beta}-{_D}-gluco- pyranose (1)$ and 3,4,5-trihydroxybenzoic acid (2) on the expression of MMP-1 in UVA-irradiated human skin fibroblasts (products), (on the) activity of MMP-1, and (on the) scavenging activities of free radicals. Compounds 1 and 2 were isolated from Melothria heterophylla (Cucurbitaceae). These compounds were found to scavenge free radicals and reactive oxygen species (ROS) and were measured to have the $SC_{50}$ values of $3.9{\mu}M\;and\;13.3{\mu}M$ against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and $4.3{\mu}M\;and\; 4.0{\mu}M$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Compounds 1 and 2 showed a dose-dependent inhibitory effect on the e):pression and activity of MMP-1 in the UVA-irradiated human skin fibroblasts. Therefore, we concluded that compounds 1 and 2 significantly inhibited MMP-1 expression at the protein level. Also, these compounds were determined to have a potent antioxidant activity. From these results, we suggest that these compounds nay be used as (a) new anti-aging agents for the photo-damaged skin.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.2
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• pp.157-167
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• 2022

In this study, we investigated the effects of heptapeptide on cellular activation and inhibition of cellular damage induced by photoaging condition in NIH3T3 fibroblasts. Cell proliferation and extracellular matrix (ECM) expression were induced by heptapeptide. The reduced cell viability under photoaging condition through ultraviolet A (UVA) irradiation was increased by heptapeptide. And UVA-induced apoptosis, matrix metalloproteinases-1 (MMP-1) expression, and reactive oxygen species (ROS) level were decreased by heptapeptide. In addition, the inhibition of transforming growth factor-β (TGF-β)/smad signaling under UVA irradiation which resulting in reduction of ECM expression was also recovered by heptapeptide. We also tested the effect of heptapeptide under another photoaging condition through heat shock, and pre-treatment of heptapeptide prevented the phosphorylation of mitogen-activated protein kinase (MAPK) and MMP-1 expression induced by heat shock. From these results, it has been shown that the heptapeptide has protective effects on fibroblasts through the up-regulation of cellular activity and through the decreasing of intracellular ROS level induced by UVA irradiation or heat shock. It is expected that the dermal protection effect of heptapeptide can be applied as a new cosmetic material in the future.