• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.113-120
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• 2019

Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma ($PPAR-{\gamma}$), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of $PPAR-{\gamma}$ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of $PPAR-{\gamma}$. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.

• Journal of Life Science
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• v.28 no.2
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• pp.265-273
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• 2018

Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.

• The korean journal of orthodontics
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• v.28 no.5 s.70
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• pp.775-782
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• 1998

The purpose of this study is to investigate the change of the EGFR mRNA expression in the rat gingival epithelium by the experimental tooth movement. We applied reciprocal force between the upper anterior teeth using NiTi open coil spring and stainless steel wire for 1, 2 3, 7 days. For the detection of EGFR mRNA, in situ hybridization was done in the tissue samples which were taken from the pressure and tension sides of teeth. The results were as follows ; 1. The expression of EGFR mRNA was increased application-time dependently. a. Day 1 mild expression on the basal and spinous cell layers b. Day 2 . moderate expression on the whole layers c. Day 3 : severe expression on the basal and spinous cell layers 4. Day 7 severe expression on the whole layers 2. The expression level of EGFR mRNA in the pressure and tension sides were similar during the whole Period of experiment except seven day application at which the cornified layer of the tension side showed moderate expression. 3. Removal of the appliance after 7-day force application lowered the level of EGRF mRNA expression. It was returned to the mild and control (rare) level at three and seven days after the removal, respectively. In conclusion, EFGR mRNA was increased by the experimental tooth movement on the rat ginigval epithelium. Up-regulation of EGFR mRNA in the gingival epithelium can be regarded as responses to the possible changes caused by the physical stersses to the oral environment to maintain the homeostatic conditions of the periodontium.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.529-535
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• 2016

Atopic dermatitis (AD) results from gene and environment interactions that lead to a range of immunological abnormalities and breakdown of the skin barrier. Protease-activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is expressed in suprabasal layers of the epidermis. PAR2 is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$ and is involved in both epidermal permeability barrier homeostasis and epithelial inflammation. In this study, we investigated the effect of lobaric acid on inflammation, keratinocyte differentiation, and recovery of the skin barrier in hairless mice. Lobaric acid blocked trypsin-induced and SLIGKV-$NH_2$-induced PAR2 activation resulting in decreased mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes. Lobaric acid reduced expression of interleukin-8 induced by SLIGKV-$NH_2$ and thymus and activation regulated chemokine (TARC) induced by tumor necrosis factor-a (TNF-${\alpha}$) and IFN-${\gamma}$ in HaCaT keratinocytes. Lobaric acid also blocked SLIGKV-$NH_2$-induced activation of ERK, which is a downstream signal of PAR2 in normal human keratinocytes (NHEKs). Treatment with SLIGKV-$NH_2$ downregulated expression of involucrin, a differentiation marker protein in HaCaT keratinocytes, and upregulated expression of involucrin, transglutamase1 and filaggrin in NHEKs. However, lobaric acid antagonized the effect of SLIGKV-$NH_2$ in HaCaT keratinocytes and NHEKs. Topical application of lobaric acid accelerated barrier recovery kinetics in a SKH-1 hairless mouse model. These results suggested that lobaric acid is a PAR2 antagonist and could be a possible therapeutic agent for atopic dermatitis.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.463-469
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• 2012

Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.50 no.2
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• pp.119-129
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• 2024

The cutaneous lymphatic system in humans plays a crucial role in draining interstitial fluid and activating the immune system. Environmental factors, such as ultraviolet light and natural aging, often affect structural changes of such lymphatic vessels, causing skin dysfunction. However, some limitations still exist because of no alternatives to animal testing. To better understand the skin lymphatic system, a biomimetic microfluidic platform, skin-lymph-on-a-chip, was fabricated to develop a novel in vitro skin lymphatic model of humans and to investigate the molecular and physiological changes involved in lymphangiogenesis, the formation of lymphatic vessels. Briefly, the platform involved co-culturing differentiated primary normal human epidermal keratinocytes (NHEKs) and dermal lymphatic endothelial cells (HDLECs) in vitro. Based on our system, Lymphanax^TM, which is a condensed Panax ginseng root extract obtained through thermal conversion for 21 days, was applied to evaluate the lymphangiogenic effect, and the changes in molecular factors were analyzed using a deep-learning-based algorithm. Lymphanax^TM promoted healthy lymphangiogenesis in skin-lymphon-a-chip and indirectly affected HDELCs as its components rarely penetrated differentiated NHEKs in the chip. Overall, this study provides a new perspective on Lymphanax^TM and its effects using an innovative in vitro system.