Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany.
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany.
Biochim Biophys Acta Gen Subj. 2018 Apr;1862(4):958-966. doi: 10.1016/j.bbagen.2018.01.017.
The epidermal growth factor receptor (EGFR) and associated receptors ERBB2 and ERBB3 are important for skin development and homeostasis. To date, ERBB4 could not be unambiguously identified in the epidermis. The aim of this study was to analyze the ERBB-receptor family with a special focus on ERBB4 in vitro in human keratinocytes and in vivo in human and murine epidermis.
We compared the transcript levels of all ERBB-receptors and the seven EGFR-ligands in HaCaT and A431 cells. ERBB-receptor activity was analyzed after epidermal growth factor (EGF) stimulation by Western blot analysis. The location of the receptors was investigated by immunofluorescence in human keratinocytes and skin. Finally, we investigated the function of ERBB4 in the epidermis of skin-specific ERBB4-knockout mice.
After EGF stimulation, all ligands were upregulated except for epigen. Expression levels of EGFR were unchanged, but all other ERBB-receptors were down-regulated after EGF stimulation, although all ERBB-receptors were phosphorylated. We detected ERBB4 at mRNA and protein levels in both human epidermal cell lines and in the basal layer of human and murine epidermis. Skin-specific ERBB4-knockout mice revealed a significantly reduced epidermal thickness with a decreased proliferation rate.
ERBB4 is expressed in the basal layer of human epidermis and cultured keratinocytes as well as in murine epidermis. Moreover, ERBB4 is phosphorylated in HaCaT cells due to EGF stimulation, and its deletion in murine epidermis affects skin thickness by decreasing proliferation.
ERBB4 is expressed in human keratinocytes and plays a role in murine skin homeostasis.
表皮生长因子受体（EGFR）和相关受体 ERBB2 和 ERBB3 对皮肤发育和稳态至关重要。迄今为止，表皮中不能明确鉴定 ERBB4。本研究旨在分析 ERBB 受体家族，特别关注体外培养的人角质形成细胞和体内人及鼠表皮中的 ERBB4。
我们比较了 HaCaT 和 A431 细胞中所有 ERBB 受体和 7 种 EGFR 配体的转录水平。用 Western blot 分析分析表皮生长因子（EGF）刺激后 ERBB 受体的活性。用人角质形成细胞和皮肤进行免疫荧光分析，研究受体的位置。最后，我们研究了皮肤特异性 ERBB4 敲除小鼠表皮中 ERBB4 的功能。
EGF 刺激后，除 epigen 外，所有配体均上调。EGF 刺激后 EGFR 表达水平不变，但所有其他 ERBB 受体均下调，尽管所有 ERBB 受体均被磷酸化。我们在人表皮细胞系和人及鼠表皮的基底层检测到 ERBB4 的 mRNA 和蛋白水平。皮肤特异性 ERBB4 敲除小鼠的表皮厚度明显减少，增殖率降低。
ERBB4 在人表皮和培养的角质形成细胞以及鼠表皮的基底层表达。此外，由于 EGF 刺激，HaCaT 细胞中 ERBB4 被磷酸化，其在鼠表皮中的缺失通过降低增殖而影响皮肤厚度。
ERBB4 在人角质形成细胞中表达，并在鼠皮肤稳态中发挥作用。
