MAD2B acts as a negative regulatory partner of TCF4 on proliferation in human dermal papilla cells

Dermal papilla cells (DPCs) are important components of hair follicles and play a critical role in hair follicle development. However, the mechanisms by which DPCs induce hair follicle development remain unclear. In the present study, we identified the mitotic arrest deficient protein MAD2B as a modifier of DPCs. Overexpression of MAD2B inhibited DPC aggregative growth and proliferation induced by the Wnt signaling activator T cell factor 4 (TCF4), and decreased TCF4-induced expression and the release of hair growth-related cytokines, including hepatocyte growth factor, insulin-like growth factor-1, and vascular endothelial growth factor in DPCs. In contrast, knockdown of MAD2B promoted TCF4-induced DPC proliferation, but did not affect the expression and secretion of cytokines by TCF4-induced DPCs. These results suggest a functional antagonism between MAD2B and TCF4 in DPC-induced hair follicle development. Mechanistically, MAD2B physically interacted with TCF4 to repress TCF4 transcriptional activity via β-catenin mediation, leading to reduced β-catenin/TCF4-dependent transactivation and Wnt signaling activity. These results demonstrate, for the first time, that MAD2B plays a negative role in TCF4-induced DPC growth and proliferation.