Androgen Receptor Transactivity Is Potentiated by TGF-β1 Through Smad3 but Checked by Its Coactivator Hic-5/ARA55 in Balding Dermal Papilla Cells

The study explored how TGF-β1 influences androgen receptor (AR) activity in dermal papilla cells from individuals with androgenetic alopecia. It was found that TGF-β1 increased AR activity by 1.9 to 2.3-fold, an effect that was dependent on Smad3, as Smad3 knockdown with siRNA stopped the TGF-β1-induced AR transactivation. Conversely, overexpression of Hic-5/ARA55, an AR coactivator, prevented TGF-β1 from significantly affecting AR activity, indicating that Hic-5/ARA55 can counteract the TGF-β1 enhancement of AR activity. These results highlight a complex interaction between TGF-β1-Smad and androgen-AR signaling in androgenetic alopecia, suggesting that the interplay between these pathways is important for normal hair cycling and may contribute to the condition's development.