Mannosylerythritol lipids ameliorate ultraviolet A-induced aquaporin-3 downregulation by suppressing c-Jun N-terminal kinase phosphorylation in cultured human keratinocytes

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-γ), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of PPAR-γ 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-γ. 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.

SH3BP4, a novel pigmentation gene, is inversely regulated by miR-125b and MITF

Our previous work has identified miR-125b as a negative regulator of melanogenesis. However, the specific melanogenesis-related genes targeted by this miRNA had not been identified. In this study, we established a screening strategy involving three consecutive analytical approaches—analysis of target genes of miR-125b, expression correlation analysis between each target gene and representative pigmentary genes, and functional analysis of candidate genes related to melanogenesis—to discover melanogenesis-related genes targeted by miR-125b. Through these analyses, we identified SRC homology 3 domain-binding protein 4 (SH3BP4) as a novel pigmentation gene. In addition, by combining bioinformatics analysis and experimental validation, we demonstrated that SH3BP4 is a direct target of miR-125b. Finally, we found that SH3BP4 is transcriptionally regulated by microphthalmia-associated transcription factor as its direct target. These findings provide important insights into the roles of miRNAs and their targets in melanogenesis.

miR-526b targets 3' UTR of MMP1 mRNA

Regulation of matrix metalloproteinases (MMPs) is important for many physiological processes involving cancers, inflammation, tissue remodeling and skin aging. Here, we report the novel finding that the expression of MMP1 mRNA is downregulated by the overexpression of miR-526b which is a member of chromosome 19 microRNA cluster (C19MC). Our analysis using reporter constructs containing the 3' untranslated region (3' UTR) of MMP1 and its mutant form showed that the region from 377-383 in the 3' UTR of MMP1 is critical for targeting by miR-526b. In addition, the expression pattern of miR-526b and MMP1 mRNA showed reverse relation between adult dermal and neonatal fibroblasts. We show for the first time that miR-526b, an miRNA belonging to C19MC, can target the 377-383 region of the MMP1 3' UTR.

Corrigendum: Comparative Analysis of Human Epidermal and Peripheral Blood gammadelta T Cell Cytokine Profiles

In this paper, the ACKNOWLEDGMENT was given incorrectly.

Comparative Analysis of Human Epidermal and Peripheral Blood gammadelta T Cell Cytokine Profiles

BACKGROUND: Human epidermal gammadelta T cells are known to play crucial roles in the defense and homeostasis of the skin. However, their precise mechanism of action in skin inflammation remains less clear. OBJECTIVE: In this study, we analyzed the cytokine expression profile of human epidermal gammadelta T cells and compared it to that of peripheral blood gammadelta T cells to investigate the specific activity of epidermal gammadelta T cells in modulating skin inflammation. METHODS: We isolated gammadelta T cells from epidermal tissue or peripheral blood obtained from healthy volunteers. Isolated gammadelta T cells were stimulated using immobilized anti-CD3 antibody and interleukin-2 plus phytohaemagglutinin, and were then analyzed using a cytokine array kit. RESULTS: Both epidermal and peripheral blood gammadelta T cells produced comparable levels of granulocyte-macrophage colony-stimulating factor, I-309, interferon-gamma, macrophage migration inhibitory factor, macrophage inflammatory protein-1alpha, and chemokine (C-C) ligand 5. The epidermal gammadelta T cells produced significantly higher levels of interleukin-4, -8, -13, and macrophage inflammatory protein-1beta than the peripheral blood gammadelta T cells did. Notably, the epidermal gammadelta T cells produced several hundred-fold higher levels of interleukin-13 than interleukin-4. CONCLUSION: These results suggest that the epidermal gammadelta T cells have a stronger potential to participate in the Th2-type response than the peripheral blood gammadelta T cells do. Furthermore, epidermal gammadelta T cells might play an important role in the pathogenesis of Th2-dominant skin diseases because of their active production of interleukin-13.

The Risk Factors of the Pre-hypertension and Hypertension of Rural Inhabitants in Chungnam-do

The purpose of this study is to investigate risk factors of pre-hypertension and hypertension in rural residents. Nine hundred and ninety four subjects aged 40-70 yrs in Chungnam-do participated in this study. The subjects (n = 824) were classified into three groups of hypertensive, pre-hypertensive, and normotensive according to the Joint National Committee (JNC)-7 criteria. The weight, body mass index (BMI), waist-hip ratio (WHR), and serum total protein, albumin, BUN, and triglyceride (TG) were positively correlated with SBP and DBP. After adjusted by age, sex and BMI, the total protein, albumin and TG were significantly correlated with SBP and DBP (p < 0.01). There was no significant difference in eating habits according to the level of blood pressure. The serum albumin, creatinine, Glu-FBS, Glu-PP l20, and triglyceride were higher in both prehypertensive and hypertensive group than in the normotensive group. However, mean serum cholesterol was not different among three blood pressure groups. In this study, the common risk factors of pre-hypertension and hyper-tension were male, age of fifties, lower education level, ex-smoking, higher drinking frequency, higher BMI, body fat %, waist circumference, WHR, serum albumin and diabetes, even though the degree of risks in these variables were higher in the hypertensive group. The higher BUN was a risk factor of prehypertension, while the family history, prediabetes, serum total protein, Glu-PP l20 and higher alcohol drinking amount were the risk factors of hypertension. This result suggests that maintaining good health habit and normal range of blood parameters as well as controlling body weight have to be paid attention in order to prevent hypertention, and further reseasch on the relationship of blood pressure and BUN are needed.