• 作者： Young Hyun Jung, Chang Woo Chae, Gee Euhn Choi, Him Cha Shin, Jae Ryong Lim, Han Seung Chang, Joonmo Park, Ji Hyeon Cho, Mo Ran Park, Hyun Jik Lee & Ho Jae Han
• 作者服務機構： 1.Biomedical Research Institute, Stempoint Co., Ltd., Seoul, 08501, South Korea 2.Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 Four Future Veterinary Medicine Leading Education & Research Center, Seoul National University, Seoul, 08826, South Korea 3.Institute for Stem Cell & Regenerative Medicine (ISCRM), Chungbuk National University, Cheongju, Chungbuk, 28644, South Korea 4.Laboratory of Veterinary Physiology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, South Korea
• 中文摘要：
• 英文摘要：
  Background
  Androgenetic alopecia (AGA) is a genetic disorder caused by dihydrotestosterone (DHT), accompanied by the senescence of androgen-sensitive dermal papilla cells (DPCs) located in the base of hair follicles. DHT causes DPC senescence in AGA through mitochondrial dysfunction. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the protective role of cyanidins on DHT-induced mitochondrial dysfunction and DPC senescence and the regulatory mechanism involved.
  
  Methods
  DPCs were used to investigate the effect of DHT on mitochondrial dysfunction with MitoSOX and Rhod-2 staining. Senescence-associated β-galactosidase activity assay was performed to examine the involvement of membrane AR-mediated signaling in DHT-induced DPC senescence. AGA mice model was used to study the cyanidins on DHT-induced hair growth deceleration.
  
  Results
  Cyanidin 3-O-arabinoside (C3A) effectively decreased DHT-induced mtROS accumulation in DPCs, and C3A reversed the DHT-induced DPC senescence. Excessive mitochondrial calcium accumulation was blocked by C3A. C3A inhibited p38-mediated voltage-dependent anion channel 1 (VDAC1) expression that contributes to mitochondria-associated ER membrane (MAM) formation and transfer of calcium via VDAC1–IP3R1 interactions. DHT-induced MAM formation resulted in increase of DPC senescence. In AGA mice models, C3A restored DHT-induced hair growth deceleration, which activated hair follicle stem cell proliferation.
  
  Conclusions
  C3A is a promising natural compound for AGA treatments against DHT-induced DPC senescence through reduction of MAM formation and mitochondrial dysfunction.
• 中文關鍵字：
• 英文關鍵字： Cyanidin 3-O-arabinoside, DHT, Androgen receptor, Mitochondrial calcium, Senescence