OBJECTIVES: EREG (epiregulin), a member of the epidermal growth factor (EGF) 
family, plays a role in inflammation, wound healing, normal physiology and 
malignancies. However, little is known about its function on hair growth.
MATERIALS AND METHODS: Cell growth assay, QPCR and immunostaining were carried 
out. Telogen-to-anagen transition and organ culture were conducted. ROS level 
was monitored by staining DCFDA.
RESULTS: We investigated the hair inductive effect of EREG and the mechanism of 
stimulation on DPCs and ORS cells during hair cycling. Whereas EREG promoted 
hair growth, EREG knockdown inhibited hair growth as evidenced by 
telogen-to-anagen transition and organ culture models. EREG was expressed in 
epidermal cells including ORS cells in vivo. EREG activated phospho-ErbB4 in 
DPCs during hair cycling and stimulated DPCs via ErbB4 activation in vitro. In 
terms of the underlying mechanism, reactive oxygen species (ROS) played a key 
role in DPC stimulation. EREG also activated phospho-EGF receptor (EGFR) in 
epidermal cells including matrix and ORS cells in vivo and stimulated ORS cells 
via EGFR activation in vitro.
CONCLUSIONS: EREG, which is released from ORS cells, activated EGFR and ErbB4 on 
epidermal cells and DPCs during hair cycling, respectively. As a result, EREG 
stimulated epidermal cells a positive feedback and DPCs via regulating ROS 
generation for hair growth. Therefore, EREG therapy may be a novel solution for 
hair loss treatment.