A study by Huang, Lin and Min-Chuan determined that bovine Lactoferrin (bLF) promoted the proliferation of dermal papilla (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-labelled bLF could bind to DP cells, and the binding was independent of lipoprotein receptor-related protein 1(LRP1), a known LF receptor. Importantly, bLF stimulated hair growth in both young and aged mice. Additionally, Huang et al. found that bLF significantly induced the expression of Wnt signalling-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. These findings suggest that bLF promotes hair growth in mice and stimulates proliferation of DP cells through Erk/Akt and Wnt signalling pathways. This study highlights a great potential of the use of bLF in developing drugs to treat hair loss (Huang et al., 2019).
Proliferation of dermal papilla cells
DP cell proliferation is crucial for the morphogenesis and growth of the hair follicles. Erk and Akt signalling pathways are the two major controllers of proliferation of many cells including DP cells. Akt plays a critical role in mediating survival signals (Huang et al., 2019). Moreover, it was reported that the Akt pathway is also involved in regulating the survival of DP cells. Consistently, it was found that bLF increases the growth of DP cells and the phosphorylation of Erk and Akt. Moreover, the Erk inhibitor PD98059 and the Akt inhibitor LY294002 significantly blocked the bLF-induced proliferative effect in DP cells. Huang et al. therefore proposed that bLF is at least partly responsible for promoting the cell proliferation in DP cells by up regulating the Erk and Akt pathways.
the topical use of bLF significantly promoted hair induction
Studies suggested that large molecules could pass through the skin via hair follicles. Therefore, it is likely that Lactoferrin can enter the bottom of hair follicles and induce DP cell proliferation. A study by Huang et al. shows that the topical use of bLF significantly promoted hair induction in C57BL/6 mice, suggesting that bLF induces hair growth and has great potential for development of anti-alopecia drugs. For clinical applications, native bLF was rapidly degraded with a half-life, in artificial gastric fluid containing pepsin, native bLF was degraded with half-life of approximately 17 min and plasma half-life of the bLF in rats was 7.8 min. For commercialization of bLF, another study showed that bLF in a liquid formulation, containing 1 mg/mL bLF, 1.74mg/mL arginine, 15% (w/v) trehalose and 0.02% (v/v) Tween 80 in 100mM sodium phosphate buffer at pH 6.5, was stable under various conditions for 6 months. The formulation for hair-growth promoting products with bLF needs to be further developed (Huang et al., 2019).
Consistent with previous findings, Wnt3a and Wnt7a can act as inductive signals to maintain the DP in the anagen state
The Wnt signalling pathway is important for the hair morphogenesis and hair cycle. Earlier research found that Wnt proteins play a critical role in normal hair follicle development and cycling. β-Catenin interacts with the members of the Lef/Tcf family of transcription factors to activate gene expression. Results from the study indicate that bLF significantly increases the mRNA levels of Wnt3a, Wnt7a, and Lef1 but not of β-catenin, Fzd7,and Gsk3b. Consistent with previous findings, Wnt3a and Wnt7a can act as inductive signals to maintain the DP in the anagen state (Huang et al., 2019). Conversely, the data showed that minoxidil increased the expression of Lef1 but not of Wnt3a and Wnt7a. It was also found that the bLF increased the expression of the Wnt pathway-related proteins, namely Wnt3a, Wnt7a, β-catenin, and Lef1, and that the Wnt pathway inhibitor XAV939 significantly reversed the bLF-induced DP cell proliferation. Therefore suggesting that Wnt signalling pathways are also involved in the bLF-mediated hair growth and that bLF and minoxidil induce hair growth by modulating different factors (Huang et al., 2019).
bLF could induce hair growth in young and aged mice. Mechanistically, bLF stimulates the proliferation of DP cells via Erk/Akt and Wnt signalling pathways, which are independent of LRP1. These findings show a great potential of the use of bLF in developing agents to treat hair loss in the future.
Huang, H. C., Lin, H., & Huang, M. C. (2019). Lactoferrin promotes hair growth in mice and increases dermal papilla cell proliferation through Erk/Akt and Wnt signalling pathways. Archives of dermatological research, 1-10