Senior Research Fellow Center, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
J Dermatol Sci. 2013 Nov;72(2):81-6. doi: 10.1016/j.jdermsci.2013.05.009. Epub 2013 Jun 13.
The epidermal growth factor (EGF) receptor/ligand system stimulates multiple pathways of signal transduction, and is activated by various extracellular stimuli and inter-receptor crosstalk signaling. Aberrant activation of EGF receptor (EGFR) signaling is found in many tumor cells, and humanized neutralizing antibodies and synthetic small compounds against EGFR are in clinical use today. However, these drugs are known to cause a variety of skin toxicities such as inflammatory rash, skin dryness, and hair abnormalities. These side effects demonstrate the multiple EGFR-dependent homeostatic functions in human skin. The epidermis and hair follicles are self-renewing tissues, and keratinocyte stem cells are crucial for maintaining these homeostasis. A variety of molecules associated with the EGF receptor/ligand system are involved in epidermal homeostasis and hair follicle development, and the modulation of EGFR signaling impacts the behavior of keratinocyte stem cells. Understanding the roles of the EGF receptor/ligand system in skin homeostasis is an emerging issue in dermatology to improve the current therapy for skin disorders, and the EGFR inhibitor-associated skin toxicities. Besides, controlling of keratinocyte stem cells by modulating the EGF receptor/ligand system assures advances in regenerative medicine of the skin. We present an overview of the recent progress in the field of the EGF receptor/ligand system on skin homeostasis and regulation of keratinocyte stem cells.
表皮生长因子（EGF）受体/配体系统刺激多种信号转导途径，并且可被各种细胞外刺激和受体间串扰信号激活。EGF 受体（EGFR）信号的异常激活存在于许多肿瘤细胞中，针对 EGFR 的人源化中和抗体和合成小分子化合物目前已在临床应用。然而，这些药物已知会引起多种皮肤毒性，如炎症性皮疹、皮肤干燥和毛发异常。这些副作用表明 EGFR 在人类皮肤中的多种依赖于 EGFR 的稳态功能。表皮和毛囊是自我更新的组织，角质形成细胞干细胞对于维持这些稳态至关重要。与 EGF 受体/配体系统相关的多种分子参与表皮稳态和毛囊发育，并且 EGFR 信号的调节会影响角质形成细胞干细胞的行为。了解 EGF 受体/配体系统在皮肤稳态中的作用是皮肤科领域的一个新兴问题，旨在改善当前的皮肤疾病治疗方法和 EGFR 抑制剂相关的皮肤毒性。此外，通过调节 EGF 受体/配体系统控制角质形成细胞干细胞可确保皮肤再生医学的进步。我们概述了 EGF 受体/配体系统在皮肤稳态和角质形成细胞干细胞调节方面的最新进展。
