Neurotrophin-3 improves retinoic acid-induced neural differentiation of skin-derived precursors through a p75NTR-dependent signaling pathway.

Skin-derived precursors (SKPs) are derived from mesoblast and can differentiate into smooth muscle cells, adipocytes, and less neuronal phenotypes. This study demonstrates that retinoic acid (RA) improves SKPs exit from self-proliferation to neural differentiation through up-regulating of NeuroD and cell-cycle regulatory protein p21, meanwhile RA also induces p75 neurotrophin receptor (p75NTR) up-regulation and apoptosis of SKPs. When treated sequentially with neurotrophin-3 (NT-3) after RA induction, the survival and neural differentiation of SKPs were enhanced significantly, and cell apoptosis induced by RA was decreased. These effects could be reversed by p75NTR inhibitor Pep5 instead of Trk receptor inhibitor K252a. The results indicate that NT-3 improves the neural differentiation of SKPs induced by RA through a p75NTR-dependent signaling pathway.