Epiregulin promotes hair growth via EGFR‐medicated epidermal and ErbB4‐mediated dermal stimulation

Abstract

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.

LncRNA018392 promotes proliferation of Liaoning cashmere goat skin fibroblasts through up-regulation of CSF1R by binding to SPI1

“…EREG (extra-epidermal regulatory protein) refers to a member of the epidermal growth factor (EGF) family, playing a certain role in in ammation and wound healing. EREG knockdown can inhibit hair growth, and EREG activate EGFR and ErbB4 on epidermal and hair papilla cells, respectively, in the hair cycle 30 . Fibronectin 1 (FN1) plays a role in cell adhesion and migration processes (e.g., embryogenesis and wound healing) as well as in a wide variety of biochemical processes.…”

Involvement of DKK1 secreted from adipose‐derived stem cells in alopecia areata

“…One such approach involves priming ASCs using hypoxia or growth factors such as EREG and PDGF. 6,10 While priming methods have the advantage of simultaneously affecting multiple genes or pathways, gene knockout offers a highly specific and precise targeting of a particular gene or pathway. Gene knockout involves a permanent modification of the genome, whereas priming typically induces transient or reversible modifications of the epigenome.…”

“…3,4 Additionally, ASCs secrete growth factors and cytokines that stimulate hair follicle growth and help hair loss prevention. [5][6][7][8][9][10][11] Despite these findings, the effectiveness of ASCs in hair growth has been somewhat limited. To enhance the hair growth potential of ASCs, researchers have explored the use of various priming factors, including growth factors, cytokines and small molecules.…”

“…To enhance the hair growth potential of ASCs, researchers have explored the use of various priming factors, including growth factors, cytokines and small molecules. [5][6][7][8][9][10][11] Additionally, we conducted gene transfection experiments, introducing three genes (PDGF-A, Sox2 and β-catenin), to facilitate the differentiation of ASCs into dermal papilla cells (DPCs) and enhance the hair growth capabilities of ASCs. 12 ASCs possess significant immunomodulatory properties, making them potential candidates for treating inflammatory or autoimmune diseases such as arthritis, colitis and other autoimmune disorders.…”

Cells, growth factors and biomaterials used in tissue engineering for hair follicles regeneration

“…Interestingly, DPCs could also regulate the cellular behavior of other HF regeneration cells. The proliferation, differentiation, and follicle formation in HF cycling and embryonic development of epithelial HFSCs are correlated with the paracrine of DPCs [ 64 , 65 ]. Moreover, DPCs even have a multilineage potential since they can undergo reprogramming to become pluripotent and then become induced pluripotent stem cells (iPSCs) [ 66 ].…”