Elevation of Hyaluronan Synthase by Magnesium Supplementation Mediated through the Activation of GSK3 and CREB in Human Keratinocyte-Derived HaCaT Cells
| Autor: | Kana Marunaka, Shokoku Shu, Mao Kobayashi, Makiko Goto, Yuji Katsuta, Yuta Yoshino, Akira Ikari |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Keratinocytes
endocrine system hyaluronan synthase QH301-705.5 magnesium hyaluronic acid Article Catalysis Cell Line Inorganic Chemistry Glycogen Synthase Kinase 3 HaCaT Cells Humans RNA Messenger Physical and Theoretical Chemistry Biology (General) Cyclic AMP Response Element-Binding Protein Molecular Biology QD1-999 Spectroscopy Skin Organic Chemistry General Medicine Up-Regulation Computer Science Applications Chemistry Dietary Supplements Hyaluronan Synthases Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 71, p 71 (2022) International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 71 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Skin barrier damage is present in the patients with hereditary disorders of the magnesium channel, but the molecular mechanism has not been fully understood. We found that the expressions of hyaluronan synthase (HAS), HAS2 and HAS3 are influenced by MgCl2 concentration in human keratinocyte-derived HaCaT cells. The exposure of cells to a high concentration (5.8 mM) of MgCl2 induced the elevation of HAS2/3 expression, which was inhibited by mRNA knockdown of nonimprinted in Prader-Willi/Angelman syndrome-like domain containing 4 (NIPAL4). Similarly, the content of hyaluronic acid (HA) was changed according to MgCl2 concentration and the expression of NIPAL4. The MgCl2 supplementation increased the reporter activities of HAS2/3, which were inhibited by NIPAL4 knockdown, indicating that the expressions of HAS2/3 are up-regulated at the transcriptional level. The reporter activities and mRNA levels of HAS2/3, and the production of HA were inhibited by CHIR-99021, a glycogen synthase kinase-3 (GSK3) inhibitor, and naphthol AS-E, a cyclic AMP-response element binding protein (CREB) inhibitor. Furthermore, the mutation in putative CREB-binding sites of promoter region in HAS2/3 genes inhibited the MgCl2 supplementation-induced elevation of promoter activity. Our results indicate that the expressions of HAS2/3 are up-regulated by MgCl2 supplementation in HaCaT cells mediated through the activation of GSK3 and CREB. Magnesium may play a pivotal role in maintaining the skin barrier function and magnesium supplementation may be useful to enhance moisturization and wound repair in the skin. |
| Databáze: | OpenAIRE |
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