5.      Role of reactive oxygen species (ROS) on androgen-inducible TGF-beta1 regulation of dermal papilla cells.
Hyeon Gyeong Yoo, Yong Jung Kang, Se Rah Lee, Hyun Keol Pyo, Oh Sang Kwon, Kyu Han Kim, Hee Chul Eun, Kwang Hyun Cho,  Department of Dermatology, Seoul National University, College of Medicine, Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital and Institute of Dermatological Science, Seoul National University, Seoul, Korea

Little is known about the roles of androgen on the regulation of redox state in the dermal papilla cells, a cellular process known to profoundly increase with aging. The androgen receptor (AR) has been reported to modulate TGF-beta1/Smad signaling and to be overexpressed in androgen-dependent scalp area of the patients with androgenetic alopecia. The rat vibrissae dermal papilla cell line (DP-6) overexpressed with AR was investigated to evaluate the role of ROS on androgen-induced increase of TGF-beta1 secretion. The AR stably-transfected DP-6 cells were incubated with R1881 or dihydrotestosterone (DHT). Flow cytometry and laser scanning confocal microscopy were undergone to measure ROS production and ELISA assay to evaluate TGF-beta1 secretion after androgen treatment. TGF-beta1 promoter activity assay was also performed whether to be influenced by pretreatment of ROS scavengers. Androgen markedly increased ROS generation and the androgen-inducible ROS augmented TGF-beta1 secretion from dermal papilla cells. Treatment with ROS scavenger or several species of inhibitors decreased ROS production and TGF-beta1 expression. Luciferase reporter assays showed suppression of TGF-beta1 promoter signaling by ROS scavengers. In conclusion, our study shows for the first time that androgen-induced TGF-beta1 accumulation in dermal papilla cells would be mediated by ROS production and prevented by antioxidants or ROS inhibitors.