Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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ER71/ETV2 Promotes Hair Regeneration from Chemotherapeutic Drug-Induced Hair Loss by Enhancing Angiogenesis

  • Lee, Tae-Jin (Department of Pathology and Immunology, Washington University School of Medicine) ;
  • Kang, Hee-Kyoung (Department of Pharmacology, School of Medicine, Jeju National University) ;
  • Berry, Jeffrey C. (Department of Medicine, Washington University School of Medicine) ;
  • Joo, Hong-Gu (College of Veterinary Medicine, Jeju National University) ;
  • Park, Changwon (Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center) ;
  • Miller, Mark J. (Department of Medicine, Washington University School of Medicine) ;
  • Choi, Kyunghee (Department of Pathology and Immunology, Washington University School of Medicine)
  • Received : 2021.01.27
  • Accepted : 2021.03.15
  • Published : 2021.09.01
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Abstract

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.

Keywords

Acknowledgement

We thank the lab members for constructive criticism and discussions of this work. This work was supported by the NIH grants HL119291 (C.P), HL149954 and HL55337 (K.C), and the 2020 Research Grant from Kangwon National University (520200067) (T. L.).

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