Pretreatment with epidermal growth factor promotes primary hair recovery in the chemotherapy-induced alopecia

Abstract

Epidermal growth factor (EGF) is not only a potent cell growth stimulant but also has a catagen-inducing effect on hair follicles. Because chemotherapeutic agents primarily damage anagen hair follicles, it would be important to investigate whether catagen inducers have beneficial effects in the prevention of chemotherapy-induced alopecia (CIA). I pretreated hair follicles with a vehicle or EGF (50 g/ml or 100 g/ml) before treatment with a chemotherapeutic agent, and I observed the severity of hair follicle damage after chemotherapy and examined the recovery patterns after CIA by using the C57BL/6 mouse model of cyclophosphamide-induced alopecia. To validate the catagen-inducing property and damage response pathway after CIA, I evaluated the hair cycle score in histological sections and the number of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells in the hair bulbs of control and EGF-treated mice. To follow gross changes as well as to assess the progression of CIA and the recovery pattern after CIA, photographs of the back skin of mice were captured and analyzed. I confirmed that topical EGF application induced a catagen-like stage in anagen hair follicles after depilation

I found that catagen-like hairs induced by EGF were protected from chemotherapy-mediated damage. Moreover, my results showed that EGF treatment favored primary hair recovery via the dystrophic anagen pathway after CIA. Given that hair follicles subjected to less severe chemotherapeutic insult enter the dystrophic anagen pathway followed by primary recovery, rather than entering the dystrophic catagen pathway followed by secondary recovery, the results of this study suggest that catagen inducers could be useful as a new alopecia-protection strategy, especially in the context of CIA.