ER71/ETV2 Promotes Hair Regeneration from Chemotherapeutic Drug-Induced Hair Loss by Enhancing Angiogenesis.
ER71/ETV2 Promotes Hair Regeneration from Chemotherapeutic Drug-Induced Hair Loss by Enhancing Angiogenesis.
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DOI：
10.4062/biomolther.2021.022
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发表时间：
2021-09-01
影响因子：
3.7
通讯作者：
Choi K
中科院分区：
文献类型：
--
作者：
Lee TJ;Kang HK;Berry JC;Joo HG;Park C;Miller MJ;Choi K
化疗引起的脱发和脱发可能会给癌症患者带来压力。头发会长回来，但有时头发会保持稀疏。因此，了解调节毛发再生的机制可能会改善化疗引起的脱发的管理。以往的研究表明，化疗药物诱导毛囊血管损伤。由于毛发生长与微血管再生有关，我们推测刺激血管生成可能会增强毛发再生。特别是，5-氟尿嘧啶（5-FU）治疗的小鼠表现出延迟的生长期开始和减少毛细血管密度相比，未经处理的对照组，表明生长期开始的延迟5-FU治疗可能是由于毛囊周围微血管的损失。我们研究了ETS转录因子ETV 2（又名ER 71），血管发育和再生的关键，是否可以促进血管生成和毛发再生在5-FU诱导的脱发小鼠模型。Tie2-Cre;在内皮细胞中缺乏Etv 2的Etv 2条件性敲除（CKO）小鼠在脱毛后呈现与对照小鼠相似的毛发再生速率。5-FU处理后，Tie 2-Cre; Etv 2 CKO小鼠显示与对照组相比毛细血管密度、生长期诱导和毛发恢复显著降低。5-FU治疗后接受慢病毒Etv 2注射的小鼠显示出显著改善的生长期诱导和毛发再生。双光子激光扫描显微镜显示，5-FU介导的血管损伤后，增强的Etv 2表达恢复了正常的血管形态。我们的数据表明，血管再生策略可能会改善化疗治疗后的头发再生。
Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.