Lithium chloride-treated human umbilical cord mesenchymal stem cells-derived exsomes promote hair growth by regulating miR-146a-5p-wnt pathway

The regulation of the hair cycle is orchestrated by a complex network of signaling pathways, and substantial evidence from extensive research indicates that exosomal miRNAs may play a pivotal role in this process. In this study, we present compelling evidence that exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs), pretreated with the Wnt pathway agonist lithium chloride (LiCl), significantly enhance hair regeneration. High-throughput sequencing was utilized to identify differentially expressed miRNAs in exosomes from both LiCl-pre-treated and untreated groups, thereby elucidating potential mechanisms underlying this phenomenon. Specifically, miR-146a-5p was found to activate the Wnt signaling pathway, thereby promoting the proliferation and migration of primary dermal papilla cells in mice. The downstream target genes of miR-146a-5p, including SFRP1, SMAD2, SMAD4, and EGFR, were predicted using bioinformatics tools and subsequently validated through experimental validation. An animal model overexpressing miR-146a-5p was constructed, demonstrating that miR-146a-5p targets SFRP1 to promote hair regeneration in mice via activation of the Wnt signaling pathway.