Lactoferrin promotes hair growth in mice and increases dermal papilla cell proliferation through Erk/Akt and Wnt signaling pathways

Hair loss affects men and women of all ages. Dermal papilla (DP) plays a crucial role in regulating the growth and cycling of hair follicles. Lactoferrin (LF) exhibits a wide range of biological functions, including antimicrobial activity and growth regulation. However, its effect on DP and its role in hair growth remain unknown. In this study, we found that bovine LF (bLF) promoted the proliferation of DP cells and enhanced the phosphorylation of Erk and Akt. The bLF-mediated proliferation was significantly blocked by the Erk phosphorylation inhibitor PD98059 or the Akt phosphorylation inhibitor LY294002. Moreover, biotin-labeled bLF could bind to DP cells, and the binding was independent of lipoprotein receptor-related protein 1, a known LF receptor. Importantly, bLF stimulated hair growth in both young and aged mice. Moreover, we also found that bLF significantly induced the expression of Wnt signaling-related proteins, including Wnt3a, Wnt7a, Lef1, and β-catenin. The bLF-mediated DP cell proliferation could be significantly reversed by the Wnt pathway inhibitor XAV939. Our findings suggest that bLF promotes hair growth in mice and stimulates proliferation of DP cells through Erk/Akt and Wnt signaling pathways. This study highlights a great potential of the use of bLF in developing drugs to treat hair loss.