Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway
© The Author(s) 2023. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences..
Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and is associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice show no phenotypes in skin or hair structures. To explore the physiological function of GSDMA, we generated conventional Gsdma1/2/3 knockout (KO) mice. We found that Gsdma1/2/3 KO mice showed significantly decreased epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate (PMA). Furthermore, we found that the alleviation of epidermal hyperplasia depends on Gsdma1/2/3 expressed specifically in keratinocytes. Mechanistically, Gsdma1/2/3 depletion downregulated epidermal growth factor receptor (EGFR) ligands, leading to decreased EGFR-Stat3/Akt signalling. These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR-Stat3/Akt pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Journal of molecular cell biology - (2023) vom: 19. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Qiyao [VerfasserIn] |
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| Links: |
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| Themen: |
Akt |
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| Anmerkungen: |
Date Revised 20.12.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/jmcb/mjad080 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM366063049 |
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. | ||
| 520 | |a Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and is associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice show no phenotypes in skin or hair structures. To explore the physiological function of GSDMA, we generated conventional Gsdma1/2/3 knockout (KO) mice. We found that Gsdma1/2/3 KO mice showed significantly decreased epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate (PMA). Furthermore, we found that the alleviation of epidermal hyperplasia depends on Gsdma1/2/3 expressed specifically in keratinocytes. Mechanistically, Gsdma1/2/3 depletion downregulated epidermal growth factor receptor (EGFR) ligands, leading to decreased EGFR-Stat3/Akt signalling. These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR-Stat3/Akt pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Akt | |
| 650 | 4 | |a EGFR | |
| 650 | 4 | |a GSDMA | |
| 650 | 4 | |a Hb-egf | |
| 650 | 4 | |a PMA | |
| 650 | 4 | |a Stat3 | |
| 650 | 4 | |a epidermal hyperplasia | |
| 700 | 1 | |a Li, Manyun |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Minli |e verfasserin |4 aut | |
| 700 | 1 | |a Xin, Ruyue |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yushu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Zhaoyu |e verfasserin |4 aut | |
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