| Autor: |
Xiuju Dai, Ken Shiraishi, Jun Muto, Hideki Mori, Masamoto Murakami, Koji Sayama |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
JID Innovations, Vol 3, Iss 4, Pp 100205- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2667-0267 |
| DOI: |
10.1016/j.xjidi.2023.100205 |
| Popis: |
Nuclear IL-33 levels are high at the epidermal edges of skin wounds and facilitate wound healing. However, IL-33−mediated regulation of keratinocyte (KC) biology during wound healing remains poorly understood. During skin-wound healing, KC migration and re-epithelialization are mediated predominantly by EGFR signaling activation and depend on the function of signal transducer and activator of transcription 3 (STAT3). We found that migrating KCs at the leading edges of mouse skin wounds exhibited concomitant induction and nuclear colocalization of IL-33 and phosphorylated STAT3. In cultured human KCs, activation of EGFR signaling caused rapid elevation of nuclear IL-33, which directly interacts with phosphorylated STAT3, promoting STAT3 activation. In vitro KC migration and wound-healing assays revealed that high nuclear IL-33 levels were required for KC migration and wound closure. KC mobility associated with a lack of suprabasal epidermal keratins and extracellular matrix degradation mediated by matrix metalloproteinases (MMPs) control cell migration at the intracellular and extracellular levels, respectively. In EGFR-activated KCs, nuclear IL-33 mediated keratin 1 and 10 downregulation and MMP9 upregulation by promoting STAT3 activation and limited MMP1, MMP3, and MMP10 induction by suppressing NF-κB transactivation. Thus, epidermal nuclear IL-33 is involved in KC migration and wound closure by regulating the STAT3 and NF-κB pathways. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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