安非雷古林
氧化应激
SOX2
伤口愈合
癌症研究
医学
细胞因子
再灌注损伤
细胞凋亡
缺血
药理学
化学
免疫学
表皮生长因子受体
内科学
转录因子
受体
生物化学
基因
作者
Yuta Inoue,Akihiko Uchiyama,Syahla Nisaa Amalia,Mai Ishikawa,Keiji Kosaka,Akiko Sekiguchi,Sachiko Ogino,Yoko Yokoyama,Ryoko Torii,Mari Hosoi,Ryoko Akai,Takao Iwawaki,María I. Morasso,Sei‐ichiro Motegi
标识
DOI:10.1016/j.jid.2023.06.202
摘要
Ischemia-reperfusion (I/R) injury is a key player in the pathogeneses of pressure ulcer formation. Our previous work demonstrated that inducing the transcription factor SOX2 promotes cutaneous wound healing through EGFR signaling pathway enhancement. However, its protective effect on cutaneous I/R injury was not well-characterized. We aimed to assess the role of SOX2 in cutaneous I/R injury and the tissue-protective effect of SOX2 induction in keratinocytes (KCs) in cutaneous I/R injury. SOX2 was transiently expressed in KCs after cutaneous I/R injury. Ulcer formation was significantly suppressed in KC-specific SOX2-overexpressing mice. SOX2 in skin KCs significantly suppressed the infiltrating inflammatory cells, apoptotic cells, vascular damage, and hypoxic areas in cutaneous I/R injury. Oxidative stress-induced mRNA levels of inflammatory cytokine expression were suppressed, and antioxidant stress factors and amphiregulin were elevated by SOX2 induction in skin KCs. Recombinant amphiregulin administration suppressed pressure ulcer development after cutaneous I/R injury in mice and suppressed oxidative stress-induced ROS production and apoptosis in vitro. These findings support that SOX2 in KCs might regulate cutaneous I/R injury through amphiregulin production, resulting in oxidative stress suppression. Recombinant amphiregulin can be a potential therapeutic agent for cutaneous I/R injury.
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