Regulation of keratinocyte signaling and function via changes in epidermal growth factor presentation
Regulation of keratinocyte signaling and function via changes in epidermal growth factor presentation
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DOI：
10.1016/j.actbio.2010.04.006
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发表时间：
2010-09-01
影响因子：
9.7
通讯作者：
Masters, Kristyn S.
中科院分区：
文献类型：
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作者：
Puccinelli, Tracy J.;Bertics, Paul J.;Masters, Kristyn S.
出于对加速皮肤伤口愈合的生物活性材料的需求，本研究描述了角质形成细胞对共价固定化表皮生长因子（EGF）的反应，以及这种生长因子物理表现的差异如何影响细胞功能。具体来说，用可溶性形式的EGF培养人角质形成细胞，以均匀模式固定或以梯度模式固定，然后分析细胞信号传导、增殖和迁移。通过改变EGF呈现的方式，角质形成细胞的行为被显著改变。角质形成细胞对固定化EGF模式的反应是高EGF受体（EGFR），低ERK1/2和Akt磷酸化，伴随着低增殖、高迁移活性和协调的细胞排列。相比之下，可溶性EGF处理的角质形成细胞EGFR较低，但ERK1/2和Akt磷酸化较高，并表现出高度增殖而非迁移的表型。角质形成细胞也对固定化EGF模式的差异作出反应，因为在固定化EGF梯度下迁移最快。更好地了解细胞与可溶性和固定化生长因子的相互作用可以帮助阐明天然愈合事件，并实现对细胞功能的更好控制，这可能对许多类型组织的伤口修复治疗的发展有用。(C) 2010材料学报Elsevier Ltd.出版。版权所有。
Motivated by the need for bioactive materials that can accelerate dermal wound healing, this work describes the responses of keratinocytes to covalently immobilized epidermal growth factor (EGF) and how differences in the physical presentation of this growth factor affect cell function. Specifically, human keratinocytes were cultured with EGF delivered in soluble form, immobilized in a homogeneous pattern or immobilized in a gradient pattern, followed by analysis of cellular signaling, proliferation and migration. By changing the manner in which EGF was presented, keratinocyte behavior was dramatically altered. Keratinocytes responded to immobilized EGF patterns with high EGF receptor (EGFR) but low ERK1/2 and Akt phosphorylation, accompanied by low proliferation, high migratory activity and coordinated cell alignment. In contrast, keratinocytes treated with soluble EGF experienced lower EGFR but higher ERK1/2 and Akt phosphorylation and displayed a highly proliferative, rather than migratory, phenotype. Keratinocytes also responded to differences in immobilized EGF patterns, as migration was fastest upon immobilized gradients of EGF. A better understanding the interaction of cells with soluble vs. immobilized growth factors can help elucidate native healing events and achieve greater control over cell function, which may be useful in the development of wound repair treatments for many types of tissues. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.