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
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DOI：
10.3390/biom10040545
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发表时间：
2020-04-01
期刊：
影响因子：
5.5
通讯作者：
Kamei, Junzo
中科院分区：
文献类型：
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作者：
Ikarashi, Nobutomo;Kaneko, Miho;Kamei, Junzo
在抗癌表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗过程中，干燥皮肤的不良反应频繁发生。在本研究中，我们进行了基础研究，以阐明EGFR-TKI导致皮肤干燥的机制，并提出新的治疗或预防措施。厄洛替尼治疗组小鼠皮肤水分含量显著低于对照组。对皮肤功能基因表达水平的评估显示，在厄洛替尼治疗组中，只有水通道水通道蛋白-3(AQP3)的表达显著降低。在表皮角质形成细胞HaCaT中加入厄洛替尼后，AQP3mRNAs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AQP3在皮肤中的表达减少，从而限制了水分从血管侧向角质层的运输。AQP3的减少也可能是由于厄洛替尼通过抑制EGFR活性而抑制ERK。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 bothAQP3mRNAand 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.