Heparin-binding EGF-like growth factor is induced by disruption of lipid rafts and oxidative stress in keratinocytes and participates in the epidermal response to cutaneous wounds
Heparin-binding EGF-like growth factor is induced by disruption of lipid rafts and oxidative stress in keratinocytes and participates in the epidermal response to cutaneous wounds
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DOI：
10.1038/sj.jid.5701069
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发表时间：
2008-03-01
影响因子：
6.5
通讯作者：
Poumay, Yves
中科院分区：
文献类型：
--
作者：
Mathay, Conny;Giltaire, Severine;Poumay, Yves
表皮内稳态和皮肤屏障的修复需要表皮角质形成细胞对其环境的改变做出反应。我们报告说，细胞压力与甲基-β-环糊精（MBCD），一种分子，提取膜胆固醇，从而破坏脂筏的结构，强烈诱导合成肝素结合EGF样生长因子（HB-EGF）在角质形成细胞通过激活p38丝裂原活化蛋白激酶。脂质筏破坏和氧化应激之间的有趣的相似之处，可以得出过氧化氢诱导p38激活和HB-EGF合成角质形成细胞。与其他研究一致，我们发现在位于受伤皮肤区域边缘的角质形成细胞中HB-EGF表达增加。分析培养的角质形成细胞暴露于rhHB-EGF，我们报告增加HB-EGF mRNA水平和分化标志物的表达的改变。有趣的是，在体内的伤口边缘和HB-EGF处理的培养物中，分化标志物发生了相同的变化。此外，皮肤样品的体外切片也诱导HB-EGF在切口边缘的表达。总之，我们的数据表明，HB-EGF的表达是角质形成细胞对挑战性环境的反应的标志物，并表明这种生长因子以类似于表皮修复过程中观察到的方式改变角质形成细胞的表型。
Epidermal homeostasis and repair of the skin barrier require that epidermal keratinocytes respond to alterations of their environment. We report that cellular stress with methyl-beta-cyclodextrin (MBCD), a molecule that extracts membrane cholesterol and thereby disrupts the structure of lipid rafts, strongly induces the synthesis of heparin-binding EGF-like growth factor (HB-EGF) in keratinocytes through the activation of p38 mitogen-activated protein kinase. Interesting parallels between lipid raft disruption and oxidative stress can be drawn as hydrogen peroxide induces p38 activation and HB-EGF synthesis in keratinocytes. Consistent with other studies, we show increased HB-EGF expression in keratinocytes located at the margin of wounded skin areas. Analyzing cultured keratinocytes exposed to rhHB-EGF, we report increased HB-EGF mRNA levels and alterations in the expression of differentiation markers. Interestingly, identical alterations in differentiation markers are shown to occur in vivo at the wound margin and in HB-EGF-treated cultures. In addition, in vitro sectioning of skin samples also induces the expression of HB-EGF at the border of the incisions. Altogether, our data suggest that expression of HB-EGF is a marker of the keratinocyte's response to a challenging environment and demonstrate that this growth factor alters the phenotype of keratinocytes in a manner similar to that observed during epidermal repair.