Identification of androgen-inducible TGF-beta1 derived from dermal papilla cells as a key mediator in androgenetic alopecia.
We attempted to establish a coculture model of human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to study the pathomechanism of AGA. Since expression of mRNA for the androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this coculture, androgen inhibited the growth of KCs by 50%, indicating that the DPCs produce diffusible growth suppressive factors into the medium in an androgen-dependent manner. Since recently increasing evidence has shown the importance of transforming growth factor-beta1 (TGF-beta1) in hair growth, we further examined the concentration of TGF-beta1 in this coculture medium after androgen treatment by ELISA assays. The results showed that androgen treatment increased the secretion of TGF-beta1 into the conditioned medium. Moreover, neutralizing anti-TGF-beta1 antibody reversed the inhibition of KC proliferation. Thus, we suggest that androgen-inducible TGF-beta1 derived from DPCs mediates hair growth suppression in AGA.
Inui
Shigeki
S
Department of Dermatology, Osaka University School of Medicine, Osaka, Japan.
Fukuzato
Yoko
Y
Nakajima
Takeshi
T
Yoshikawa
Kunihiko
K
Itami
Satoshi
S
D000505:Alopecia / Q000209:etiology* / Q000473:pathology; D000728:Androgens / Q000378:metabolism*; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D015741:Metribolone / Q000494:pharmacology; D009994:Osmolar Concentration; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D000728:Androgens; D000906:Antibodies; D017077:Culture Media, Conditioned; D011944:Receptors, Androgen; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015741:Metribolone