• 대한화장품학회지
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• 제34권1호
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• pp.1-8
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• 2008

피부장벽을 포함한 표피층은 인체의 조직 가운데에서도 가장 역동적인 기관이다. 다시 말해서 끊임없이 새로운 표피세포의 형성, 분화 및 탈각과정이 반복되면서 표피항상성(epidermal homeostasis)을 유지한다. 표피항상성은 피부기능 가운데 가장 주요한 기능인 permeability barrier homeostasis의 확립으로 연결된다. Permeability barrier homeostasis는 각질층에서 이루어지며 이를 형성하고 유지하기 위해 매우 정교하게 조절되어야 한다. 표피항상성을 조절하는 핵심 조절인자로서 nuclear hormone receptor(NHR)가 중심에 있음이 최근 다양한 연구를 통해 입증되었다. 이들은 각질세포 특이적인 단백질, 즉, involucrin, loricrin 및 trans-glutaminase 1(TG 1) 등의 발현을 유전자 수준에서 조절할 뿐 아니라 표피 지질성분의 생합성을 증가시키는 등 피부장벽을 구성하는 brick 및 mortar의 생성과 유지에 핵심적 역할을 하는 것으로 알려졌다. NHR 가운데 peroxisome proliferator activator receptor(PPAR)와 liver X receptor(LXR)의 activator/ligands가 리놀레인산 등 지방산, leukotriene, prostanoid 및 oxygenated sterol 등이 지질대사과정에서 형성된 지질 종류인 까닭에 liposensor로도 알려지고 있다. 따라서 liposensor들을 비롯한 PPAR과 LXR activator/ligands들은 피부장벽기능이 저해된 아토피성 피부를 포함하여 건조피부를 관리하는 epidermotherapy의 수단으로서 잠재적 가능성이 있다고 생각된다.

• 대한한방소아과학회지
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• 제31권3호
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• pp.14-23
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• 2017

Objectives This study is conducted to evaluate skin fat barrier formation of Hataedock using the Coptis japonica & Glycyrrhiza uralensis extract. Methods The 3-week-old NC/Nga mice were divided into 3 groups: control group (Ctrl), Hataedock-treated group that uses the Coptis japonica & Glycyrrhiza uralensis (CGT) extract, and Hataedock-treated group that uses Bifidobacterium (BBT). After 2 weeks, changes in immunohistochemicals, and skin-lipid-barrier regulators were observed for the effects of Hataedock. Results In CGT group, loricrin-positive reaction has been increased by 231%, along with involucrin-positive reaction by 90%, filaggrin-positive reaction by 143%, and ASM-positive reaction by 341% in the stratum corneum. Conclusions Hataedock, using the extract of Coptis japonica & Glycyrrhiza uralensis, increased the expression of proteins promoting keratinocyte differentiation. This leads into conclusion that Hataedock may increase the keratinocyte formation and function which promotes skin barrier formation.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.525-530
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• 2015

Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes. When human keratinocytes were grown in 1.2 mM calcium with vitamin C ($50{\mu}g/ml$) for 11 days, bulk ceramide content significantly increased in conjunction with terminal differentiation of keratinocytes as compared to vehicle controls (1.2 mM calcium alone). Synthesis of the ceramide fractions was enhanced by increased de novo ceramide synthesis pathway via serine palmitoyltransferase and ceramide synthase activations. Moreover, sphingosine-1-phosphate (S1P) hydrolysis pathway by action of S1P phosphatase was also stimulated by vitamin C supplementation, contributing, in part, to enhanced ceramide production. However, activity of sphingomyelinase, a hydrolase enzyme that converts sphingomyelin to ceramide, remained unaltered. Taken together, we demonstrate that vitamin C stimulates ceramide production in keratinocytes by modulating ceramide metabolicrelated enzymes, and as a result, could improve overall epidermal barrier function.

• 대한화장품학회지
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• 제39권1호
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• pp.75-81
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• 2013

Chrysin (5,7-dihydroxyflavone)은 프로폴리스, 꿀 같은 음식과 다양한 식물에 존재하는 천연 플라보노이드이다. Chrysin은 항산화, 항노화, 항염, 항암 효과 등 다양한 생물학적 효과를 가진다고 알려져 있다. 이 연구에서, 우리는 사람의 각질형성세포에서 chrysin이 VDR을 통한 transcriptional activity에 미치는 영향을 dual-luciferase assay을 통하여 살펴보았다. Chrysin은 농도 의존적으로 VDR을 통한 transcriptional activity를 증가시켰다. Quantitative real time PCR을 통해 chrysin이 사람의 각질형성세포에서 VDR mRNA의 발현을 증가시킴을 확인하였다. 또한, chrysin이 각질형성세포의 분화 마커인 keratin 10, involucrin 그리고 filaggrin의 mRNA 발현을 증가시킴을 확인하였다. 이러한 연구 결과는 chrysin이 VDR을 통한 transcriptional activity를 조절하여 각질형성세포의 분화를 촉진시킬 수 있다는 것을 시사한다.

• Biomolecules & Therapeutics
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• 제18권3호
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• pp.280-285
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• 2010

Glycosaminoglycans (GAGs) and chitosan have been used as matrix materials to support the dermal part of skin equivalent which is used for both pharmacological and toxicological evaluations of drugs potentially used for dermatological diseases. However, their biological roles of GAGs and chitosan in the skin equivalent are still unknown. In the present study, we evaluated whether GAGs and chitosan directly affect keratinocyte stem cells (KSCs) and their transit-amplifying cells (TA cells). Among supporting matrix materials, chitosan significantly increased the number of ${\alpha}6$ $integrin^{high}/CD71^{high}$ human keratinocyte TA cells by 48.5%. In quantitative real-time RT-PCR analysis, chitosan significantly increased CD71 and CD200 gene transcription whereas not ${\alpha}6$ integrin. In addition, the level of the gene transcription of both keratin 1 (K1) and K10 in the chitosan-treated human keratinocytes was significantly lower than those of control, suggesting that chitosan inhibit keratinocyte differentiation. We also found that N-acetyl-D-glucosamine (NAG) and $\beta$-(1-4)-linked D-glucosamine (D-glc), two components of chitosan, have no effect on the expression of CD71, K1, and K10, suggesting that each monomer component of chitosan is not enough to regulate the number of epidermal keratinocyte lineage. Conclusively, chitosan increases keratinocyte TA cell population which may contribute to the cellular mass expansion of the epidermal part of a skin equivalent system.

• 대한화장품학회지
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• 제49권1호
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• pp.75-85
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• 2023

본 연구에서는 7 개의 아미노산으로 이루어진 헵타펩타이드의 Lgr5 binding에 따른 인체 모낭 구성 세포의 활성에 대한 영향을 확인하였다. 표면 플라즈몬 공명(surface plasmon resonance, SPR) 시스템을 이용하여 헵타펩타이드가 Lgr5에 결합하는 것을 확인하였다. 인체 모유두세포(human hair follicle dermal papilla cell, HHFDPC)에 헵타펩타이드를 처리한 결과, 농도 의존적인 세포 증식이 나타났으며 β-catenin의 세포 내핵 이동 및 하위 유전자인 LEF1, Cyclin-D1, c-Myc의 발현 증가가 관찰되었다. 그리고 세포 증식 기전 관련 인자인 Akt와 ERK의 인산화 수준이 증가되었으며, 성장인자인 hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF) 발현이 유도되었다. 또한 인체 모모세포(human hair germinal matrix cell, HHGMC)의 분화 관련 전사 인자와 인체 외모근초세포(human hair outer root sheath cell, HHORSC)의 분화 표지 인자들도 헵타펩타이드 처리 시 높은 발현율을 보였다. 추가적으로 우리는 헵타펩타이드의 인체 모낭줄기세포(human hair follicle stem cell, HHFSC) 분화에 대한 영향을 조사하였다. 그 결과, HHFSC 표지인자들의 mRNA와 단백질 수준이 감소하였고 반면에 분화 표지인자들은 증가하였다. 상기의 결과들은 헵타펩타이드가 인체 모낭 구성 세포에서 Wnt/β-catenin 경로를 촉진시켜 증식 또는 분화를 유도할 수 있음을 보여준다. 이를 토대로 종합해 볼 때, 본 연구의 헵타펩타이드는 모발 성장을 유도하고 탈모 개선에 도움을 줄 수 있는 기능성 원료로 사용될 수 있을 것으로 보인다.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.296-307
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• 2017

In spite of frequent usage of primary human foreskin keratinocytes (HFKs) in the study of skin biology, senescence-induced block-age of in vitro proliferation has been a big hurdle for their effective utilization. In order to overcome this passage limitation, we first isolated ten HFK lines from circumcision patients and successfully immortalized four of them via a retroviral transduction of high-risk human papillomavirus (HPV) E6 and E7 oncogenes. We confirmed expression of a keratinocyte marker protein, keratin 14 and two viral oncoproteins in these immortalized HFKs. We also observed their robust responsiveness to various exogenous stimuli, which was evidenced by increased mRNA expression of epithelial differentiation markers and pro-inflammatory genes in response to three reactive chemicals. In addition, their applicability to cytotoxicity assessment turned out to be comparable to that of HaCaT cells. Finally, we confirmed their differentiation capacity by construction of well-stratified three dimensional skin cultures. These newly established immortalized HFKs will be valuable tools not only for generation of in vitro skin disease models but also for prediction of potential toxicities of various cosmetic chemicals.

• Journal of Ginseng Research
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• 제36권1호
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• pp.68-77
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• 2012

In this study, we investigated the protective effects of processed Panax ginseng, sun ginseng (SG) against the UVB-irradiation on epidermal keratinocytes and dermal fibroblasts. Pretreatment of SG in HaCaT keratinocytes and human dermal fibroblasts reduced UVB-induced cell damage as seen by reduced lactate dehydrogenase release. We also found that SG restored the UVB-induced decrease in anti-apoptotic gene expression (bcl-2 and bcl-xL) in these cells, indicating that SG has an anti-apoptotic effect and thus can protect cells from cell death caused by strong UVB radiation. In addition, SG inhibited the excessive expression of c-jun and c-fos gene by the UVB in HeCaT cells and human dermal fibroblasts. We also demonstrated that SG may exert an anti-inflammatory activity by reducing the nitric oxide production and inducible nitric oxide synthase mRNA synthesis in HaCaT keratinocytes and human dermal fibroblasts. This was further supported by its inhibitory effects on the elevated cyclooxygenase-2 and tumor necrosis factor-${\alpha}$ transcription which was induced by UVB-irradiation in HaCaT cells. In addition, SG may have anti-aging property in terms of induction of procollagen gene expression and inhibition of the matrix metalloprotease-1 gene expression caused by UVB-exposure. These findings suggest that SG can be a potential agent that may protect against the dermal cell damage caused by UVB.

• Nutritional Sciences
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• 제9권3호
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• pp.212-226
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• 2006

The involvement of arachidonic acid (AA) metabolizing enzyme, lipoxygenase (LOX), in the development of particular tumors in humans has gradually been acknowledged and LOX has emerged as a novel target to prevent or treat human cancers. In the mouse skin carcinogenesis model, which provides an excellent model to study multistage nature of human cancer development, many studies have shown that some of the LOXs are constitutively upregulated in their expression. Moreover, application of LOX inhibitors effectively reduced tumor burdens, which implicates the involvement of LOX in mouse skin tumor development as well. 8S-LOX is a recently cloned LOX, which is specifically expressed in mouse skin after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment but not in normal skin. Unlike other members of the LOX 'family' expressed in mouse skin, this TPA-induced expression of 8S-LOX is prominent only in the skin of the TPA tumor promotion-sensitive strains of mice (SENCAR, CD-1, and NMRI) but not in the promotion-resistant C57BL/6J mice. This is a very unique phenomenon among strains of mice. Constitutive upregulation of 8S-LOX was also found in early stage papillomas and the expression was gradually reduced as the tumors became malignant. Based on these observations, it has been thought that 8S-LOX is involved in TPA-induced tumor promotion as well as in tumor conversion from papillomas to carcinomas. In accordance with this hypothesis, several studies have suggested possible roles of 8S-hydroxyeicosatetraenoic acid (HETE), an AA metabolite of 8S-LOX, in mouse skin tumor development. A clastogenic activity of 8S-HETE was demonstrated in primary keratinocytes and a close correlation between the levels of etheno-DNA adducts and 8S-HETE during skin carcinogenesis was also reported. On the other hand, it has been reported that 8S-LOX protein expression is restricted to a differentiated keratinocyte compartment Moreover, reported findings on the ability of 8S-HETE to cause keratinocyte differentiation appear to be contrary to the procarcinogenic features of the 8S-LOX expression, presenting a question as to the role of 8S-LOX during mouse skin carcinogenesis. In this review, molecular and biological features of 8S-LOX as well as current views on the functional role of 8S-LOX/8S-HETE during mouse skin carcinogenesis are presented.

• 한국식품과학회지
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• 제40권6호
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• pp.686-690
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• 2008

In vivo에서 8주간의 UVB 처리에 의해 유발되는 피부 장벽 기능 손상에 대한 커큐민의 보호 효능을 관찰한 결과, UVB에 의해 유도되는 경표피 수분손실량의 증가와 비정상적인 각질 세포의 증식이 커큐민의 섭취에 의해 억제됨을 확인하여 커큐민이 피부 장벽 손상을 방어하고 피부 장벽 기능이 정상적으로 작용할 수 있도록 도움을 주는 것을 알 수 있었다. 커큐민의 피부 장벽기능 보호 작용 기전을 살펴보기 위하여 각질형성세포주를 이용하여 피부 장벽 조절인자에 대한 커큐민의 작용을 평가한 결과 커큐민은 filaggrin과 SPT의 발현을 농도 의존적으로 증가시킴을 확인하였으며, 이를 통하여 커큐민이 각질형성세포의 정상적인 분화를 촉진하고 세라마이드 합성에 영향을 미침으로써 피부 장벽 기능을 강화하는 효능이 있음을 추정할 수 있었다. 이상의 결과로부터 커큐민이 피부 장벽 보호 또는 개선 효능을 갖는 새로운 미용 식품 소재로써 이용 가능성이 높음을 알 수 있다. 다만 식품 소재로써 커큐민을 활용하기 위해서는 그간 보고된 커큐민의 낮은 bioavailability에 대한 연구를 참고하여 임상에서 유효한 용량을 설정하기 위한 연구가 더 이루어져야 할 것이다.