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Baicalein and Salvia officinalis Extract Upregulate Transglutaminase 1 mRNA Expression via the Activation of Transient Receptor Potential Channel V4

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Journal of Cosmetics, Dermatological Sciences and Applications 2022年第1期12卷 1-9页

作者： Akihiro Aioi ryuta muromoto Tadashi Matsuda Septem-Soken 2-4-27 Dojima Kita-ku Osaka Japan Laboratory of Immunology Faculty of Pharmaceutical Sciences Hokkaido University Kita 12 Nishi 6 Kita-ku Sapporo Japan

Background: It is important to maintain skin homeostasis for cosmetic and medical reasons. Many ceramide-related ingredients and cosmetics have been developed to improve the skin barrier function and skin hydration. Similar to extracellular lipids, the cornified envelope, which is a structure formed beneath the plasma membrane, contributes to the skin barrier function as a scaffold for extracellular lipids. Therefore, in this study, we focused on transglutaminase 1 (TGM1) which is the key enzyme for formation of the cornified envelope Objective: The objectives of this study were to identify compounds that could upregulate the expression of TGM1 and evaluate their underlying action mechanisms. Methods: Expression of the transient receptor potential channel vanilloid subfamily member 4 (TRPV4) at the mRNA and protein levels was estimated by PCR and western blotting. Effects of baicalein and Salvia officinalis (SO) extract on TGM1 mRNA expression were measured by PCR. The involvement of TRPV4 in TGM1 mRNA expression was evaluated by the inhibition and silencing of TRPV4. Results: TRPV4 was expressed in both basal cell-like HaCaT cells and suprabasal cell-like HaCaT cells. Baicalein and SO extract upregulated TGM1 mRNA expression in basal cell-like HaCaT cells. However, inhibition and silencing of TRPV4 abrogated the effects of baicalein and SO extract. Conclusion: Baicalein and SO extract upregulated the expression of TGM1 mRNA via the activation of TRPV4, suggesting that it may improve the skin barrier function by enhancing cornified envelope formation.

关键词： Transient Receptor Potential Channels Transglutaminase 1 Salvia officinalis Skin Homeostasis

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Current understanding of the role of tyrosine kinase 2 signaling in immune responses

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World Journal of Biological Chemistry 2022年第1期13卷 1-14页

作者： ryuta muromoto Kenji Oritani Tadashi Matsuda Department of Immunology Graduate School of Pharmaceutical SciencesHokkaido UniversitySapporo 060-0812Japan Department of Hematology International University of Health and WelfareNarita 286-8686Japan

Immune system is a complex network that clears pathogens,toxic substrates,and cancer *** self-antigens from non-self-antigens is critical for the immune cell-mediated response against foreign *** innate immune system elicits an early-phase response to various stimuli,whereas the adaptive immune response is tailored to previously encountered *** immune responses,B cells differentiate into antibody-secreting cells,while naïve T cells differentiate into functionally specific effector cells[T helper 1(Th1),Th2,Th17,and regulatory T cells].However,enhanced or prolonged immune responses can result in autoimmune disorders,which are characterized by lymphocytemediated immune responses against *** transduction of cytokines,which regulate the inflammatory cascades,is dependent on the members of the Janus family of protein *** kinase 2(Tyk2)is associated with receptor subunits of immune-related cytokines,such as type I interferon,interleukin(IL)-6,IL-10,IL-12,and *** studies on the therapeutic effects and the underlying mechanisms of Tyk2 inhibitors in autoimmune or chronic inflammatory diseases are currently *** review summarizes the findings of studies examining the role of Tyk2 in immune and/or inflammatory responses using Tyk2-deficient cells and mice.

关键词： Tyrosine kinase 2 Cytokines Signal transduction Immune system Inflammation

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Porcine Placenta Extract Reduced Wrinkle Formation by Potentiating Epidermal Hydration

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Journal of Cosmetics, Dermatological Sciences and Applications 2021年第2期11卷 101-109页

作者： Akihiro Aioi ryuta muromoto Sho Mogami Megumi Nishikawa Shigeyuki Ogawa Tadashi Matsuda New Business Development Division Septem-Soken Osaka Japan Department of Immunology Faculty of Pharmaceutical Sciences Hokkaido University Sapporo Japan

Background: Placenta extract is used as an alternative medicine especially in Asian countries as it is a rich reservoir of diverse bioactive molecules. The effects of placenta extract on skin conditions have been previously reported, however, the mechanism underlying for reduced wrinkle formation remains unclear. Objective: The primary objective of this study was to determine whether the continuous application of porcine placenta extract (PPE) alleviates wrinkle formation in humans and explore the underlying mechanism. Methods: Wrinkle formation, skin hydration, and skin elasticity were measured in 15 volunteers at weeks 0 and 6 after continuous application of a gel containing PPE. The production of type I collagen and hyaluronic acid from fibroblasts and keratinocytes, respectively, were measured using ELISA. Expression levels of ceramide synthase 3 (CERS3), filaggrin (FLG), transglutaminase 1 (TGM1), and kallikrein-7 (KLK7) were evaluated by quantitative real-time PCR. Results: The wrinkle index was significantly reduced to 72.1% after a 6-week of applying the PPE gel, along with a significant increase in skin hydration to 126.5%. Type I collagen production from fibroblasts was enhanced slightly but significantly following treatment with PPE. PPE accelerated the expression of CERS3 (1.85-fold), FLG (1.35-fold), TGM1 (1.76-fold), and KLK7 (1.62-fold). Conclusion: Treatment with PPE alleviates wrinkle formation and simultaneously enhances skin hydration, which is induced via the accelerated expression of moisturizing-related proteins. These findings suggest that PPE is effective for combating dryness-induced wrinkle formation.

关键词： Porcine Placenta Wrinkle Formation Moisturizing-Related Proteins Keratinocyte Differentiation

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Porcine Placenta Extract Enhances Ceramide Synthase 3 Expression through the PPARδ/ILK/Akt/mTOR/STAT3 Pathway

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Journal of Cosmetics, Dermatological Sciences and Applications 2022年第3期12卷 131-144页

作者： Akihiro Aioi ryuta muromoto Jun-ichi Kashiwakura Sho Mogami Megumi Nishikawa Shigeyuki Ogawa Tadashi Matsuda Septem-Soken 2-4-27 Dojima Kita-ku Osaka Japan Laboratory of Immunology Faculty of Pharmaceutical Sciences Hokkaido University Sapporo Japan

Porcine placenta extract (PPE) is widely accepted as an ingredient in complementary and alternative medicine and previous studies have reported its availability, however, its underlying action mechanism remains unclear. In this study, we investigated the underlying mechanism of PPE-induced ceramide synthase 3 upregulation. PPE enhanced the expression of ceramide synthase 3 at both the mRNA and protein levels in HaCaT cells. Moreover, PPE-induced ceramide synthase3 upregulation was suppressed by the Akt inhibitor, suggesting the involvement of Akt in the underlying mechanism. As the PI3K inhibitor did not affect PPE-induced ceramide synthase 3 upregulation, the factors upstream of Akt were estimated. Inhibition and small interfering RNA experiments demonstrated that the peroxisome proliferator-activated receptors δ (PPARδ) and integrin-linked kinase (ILK) are involved in the phosphorylation of Akt. Next, we explored the factors downstream of Akt and found that PPE induced phosphorylation of the STAT3 while PPE-induced upregulation of ceramide synthase 3 was significantly suppressed by the inhibitor of the mTOR, suggesting that the mTOR/STAT3 pathway is involved in the downstream of Akt. These results demonstrate that PPE upregulates CerS3 expression via the PPARδ/ILK/Akt/mTOR/STAT3 pathway.

关键词： Porcine Placenta Ceramide Synthase 3 Signaling Pathway

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Signal transducer and activator of transcription 3 regulation by novel binding partners

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World Journal of Biological Chemistry 2015年第4期6卷 324-332页

作者： Tadashi Matsuda ryuta muromoto Yuichi Sekine Sumihito Togi Yuichi Kitai Shigeyuki Kon Kenji Oritani Department of Immunology Graduate School of Pharmaceutical SciencesHokkaido University Department of Hematology and Oncology Graduate School of Medicine Osaka University

Signal transducers and activators of transcription(STATs) mediate essential signals for various biological processes,including immune responses,hematopoiesis,and neurogenesis. STAT3,for example,is involved in the pathogenesis of various human diseases,including cancers,autoimmune and inflammatory disorders. STAT3 activation is therefore tightly regulated at multiple levels to prevent these pathological conditions. A number of proteins have been reported to associate with STAT3 and regulate its activity. These STAT3-interacting proteins function to modulate STAT3-mediated signaling at various steps and mediate the crosstalk of STAT3 with other cellular signaling pathways. This article reviews the roles of novel STAT3 binding partners such as DAXX,zipperinteracting protein kinase,Krüppel-associated box-associated protein 1,Y14,PDZ and LIM domain 2 and signal transducing adaptor protein-2,in the regulation of STAT3-mediated signaling.

关键词： Janus kinase/signal transducer and activator of tr

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Porcine Placenta Extract Reduced Wrinkle Formation by Potentiating Epidermal Hydration

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Journal of Cosmetics, Dermatological Sciences and Applications（化妆品、皮肤病及应用期刊） 2021年第2期

作者： Akihiro Aioi ryuta muromoto Sho Mogami Megumi Nishikawa Shigeyuki Ogawa Tadashi Matsuda

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Porcine Placenta Extract Enhances Ceramide Synthase 3 Expression through the PPARδ /ILK/Akt/mTOR/STAT3 Pathway

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Journal of Cosmetics, Dermatological Sciences and Applications（化妆品、皮肤病及应用期刊） 2022年第3期

作者： akihiro aioi ryuta muromoto jun-ichi kashiwakura sho mogami megumi nishikawa shigeyuki ogawa tadashi matsuda

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