表皮生长因子受体酪氨酸激酶抑制剂厄洛替尼通过降低水通道蛋白-3的表达诱导皮肤干燥。

PubMed ID
G H
发表日期 2020年04月

原始出处 生物分子
Biomolecules
作者 Ikarashi  Nobutomo  Kaneko  Miho  Watanabe  Tomofumi  Kon  Risako  Yoshino  Makana  Yokoyama  Takatoshi  Tanaka  Riho  Takayama  Naoya  Sakai  Hiroyasu  Kamei  Junzo 

文献标题 表皮生长因子受体酪氨酸激酶抑制剂厄洛替尼通过降低水通道蛋白-3的表达诱导皮肤干燥。
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Induces Dry Skin via Decreased in Aquaporin-3 Expression.
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Induces Dry Skin via Decreased in Aquaporin-3 Expression.

文献摘要

在使用抗癌表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗期间,干性皮肤的不良反应经常发生。本研究对EGFR-TKI诱导皮肤干燥的机制进行了基础性研究,并提出了新的治疗或预防措施。厄洛替尼治疗组小鼠的皮肤含水量显著低于对照组。对皮肤功能基因表达水平的评估显示,厄洛替尼治疗组只有水通道水通道蛋白-3(AQP3)的表达显著降低。当厄洛替尼加入表皮角质形成细胞HaCaT细胞后,aqp3mrna和蛋白的表达水平均下降。厄洛替尼治疗还显著降低了HaCaT细胞和小鼠皮肤中磷酸化EGFR和磷酸化细胞外信号调节激酶(ERK)的表达水平。厄洛替尼引起的皮肤干燥可能是由于皮肤中AQP3的表达减少,从而限制了水从血管侧向角质层侧的传输。AQP3的减少也可能是由于ERK通过erlotinib抑制EGFR活性而受到抑制。因此,增加AQP3表达的物质可能对厄洛替尼诱导的皮肤干燥有效。


An adverse reaction of dry skin occurs frequently during treatment with anticancer epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In this study, we conducted basic research to clarify the mechanism of EGFR-TKI-induced dry skin and propose new treatments or preventative measures. Dermal water content was significantly lower in the erlotinib-treated mice than in the control group. An assessment of the expression levels of functional genes in the skin revealed that only the expression of the water channel aquaporin-3 (AQP3) was significantly decreased in the erlotinib-treated group. When erlotinib was added to epidermal keratinocyte HaCaT cells, the expression levels of both AQP3 mRNA and protein decreased. Erlotinib treatment also significantly decreased the expression levels of phospho-EGFR and phospho-extracellular signal-regulated kinase (ERK), both in HaCaT cells and mouse skin. Dry skin due to erlotinib may be caused by the decreased expression of AQP3 in the skin, thereby limiting water transport from the vascular side to the corneum side. The decrease in AQP3 may also be attributable to ERK suppression via inhibition of EGFR activity by erlotinib. Therefore, substances that increase AQP3 expression may be effective for erlotinib-induced dry skin.

An adverse reaction of dry skin occurs frequently during treatment with anticancer epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In this study, we conducted basic research to clarify the mechanism of EGFR-TKI-induced dry skin and propose new treatments or preventative measures. Dermal water content was significantly lower in the erlotinib-treated mice than in the control group. An assessment of the expression levels of functional genes in the skin revealed that only the expression of the water channel aquaporin-3 (AQP3) was significantly decreased in the erlotinib-treated group. When erlotinib was added to epidermal keratinocyte HaCaT cells, the expression levels of both AQP3 mRNA and protein decreased. Erlotinib treatment also significantly decreased the expression levels of phospho-EGFR and phospho-extracellular signal-regulated kinase (ERK), both in HaCaT cells and mouse skin. Dry skin due to erlotinib may be caused by the decreased expression of AQP3 in the skin, thereby limiting water transport from the vascular side to the corneum side. The decrease in AQP3 may also be attributable to ERK suppression via inhibition of EGFR activity by erlotinib. Therefore, substances that increase AQP3 expression may be effective for erlotinib-induced dry skin.


获取全文 10.3390/biom10040545