Androgen-inducible TGF-β1 from balding dermal papilla cells inhibits epithelial cell growth:: a clue to understanding paradoxical effects of androgen on human hair growth
Androgen-inducible TGF-β1 from balding dermal papilla cells inhibits epithelial cell growth:: a clue to understanding paradoxical effects of androgen on human hair growth
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DOI：
10.1096/fj.02-0043fje
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发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
Itami, S
中科院分区：
文献类型：
--
作者：
Inui, S;Fukuzato, Y;Itami, S
本研究尝试建立人雄激素性脱发（阿加）毛乳头细胞（DPC）与角质形成细胞（KCs）共培养体系，探讨雄激素在毛发生长调节中的作用。雄激素对KCs与阿加来源的DPC共培养的生长无明显影响。由于雄激素受体（AR）mRNA在体外传代培养的DPC中表达下降，我们将AR表达载体瞬时转染DPC，并将其与KC共培养。在这种改良的共培养中，雄激素显著抑制KCs的生长，抑制率接近50%，表明AR的过表达可以恢复体内DPC对雄激素的反应性。我们发现，雄激素刺激TGF-β 1 mRNA的表达在共培养的DPC。ELISA分析表明，雄激素治疗增加了条件培养基中总TGF-β 1和活性TGF-β 1的分泌。此外，中和性抗TGF-β 1抗体以剂量依赖性方式逆转雄激素引起的KC生长抑制。这些发现表明，雄激素诱导的TGF-β 1来自DPC的阿加参与上皮细胞生长抑制在我们的共培养系统，提供线索，了解矛盾的影响雄激素对人类头发生长。
We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from AGA. Because the expressions of mRNA of 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 modified coculture, androgen significantly suppressed the growth of KCs by similar to50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of AGA is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.