title: Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.
abstract: BACKGROUND
  Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA), a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo.
  
  
  RESULTS
  Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP). VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX), a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl(2) also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice.
  
  
  CONCLUSIONS
  Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth.
authors.affiliation: Translational Research Center for Protein Function Control, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
authors.forename: Soung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Juyong
authors.initials: J
authors.lastname: Yoon
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Shin
authors.forename: Muhamad
authors.initials: M
authors.lastname: Zahoor
authors.forename: Hyoung Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Phil June
authors.initials: PJ
authors.lastname: Park
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Park
authors.forename: Do Sik
authors.initials: do S
authors.lastname: Min
authors.forename: Hyun-Yi
authors.initials: HY
authors.lastname: Kim
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism*; D000505:Alopecia / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020405:Dermis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000091344:Filaggrin Proteins; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053569:Keratin-15 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008914:Minoxidil / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; C116015:KRT15 protein, human; D053569:Keratin-15; D008565:Membrane Proteins; D051153:Wnt Proteins; D051176:beta Catenin; C064554:loricrin; D008914:Minoxidil; D014635:Valproic Acid; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D000469:Alkaline Phosphatase