Human lactoferrin (hLF), a glycoprotein of the transferrin family, has recently been shown to stimulate wound repair through its antimicrobial effect and inflammation modulation. A recent study with several non-skin cell lines indicated that hLF may also have a stimulatory effect on cell proliferation. To explore the role of hLF in wound healing, we used recombinant human lactoferrin (holo-rhLF), derived from transgenic rice, to examine the effects of holo-rhLF on cell proliferation, migration, attachment, and survival in a human primary skin fibroblast culture system. This study revealed that holo-rhLF not only significantly stimulates fibroblast proliferation but also has synergistic effects with fibroblast growth factor-2 and antagonistic effects with transforming growth factor-β1 on cell proliferation. Furthermore, using a chamber migration assay, our results demonstrate that holo-rhLF promotes fibroblast migration in a dosage-dependent manner. More importantly, holo-rhLF significantly increased cell viability and protected cells from death when they were stressed by either serum depletion or 12-O-tetradecanoylphorbol-13-acetate exposure. No significant effect was observed on cell attachment. In conclusion, these findings reveal the multiple functions of holo-rhLF in human skin fibroblasts and indicate its potential application in wound therapy by enhancing cell proliferation and migration as well as protecting cells from apoptosis.
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