A rice-derived recombinant human lactoferrin stimulates fibroblast proliferation, migration, and sustains cell survival

• Published in: Wound repair and regeneration 2010-01, Vol.18 (1), p.123-131
• Main Authors: Tang, Ling, Cui, Tengjiao, Wu, James J., Liu-Mares, Wen, Huang, Ning, Li, Jie
• Format: Article
• Language: English
• Subjects: Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Synergism; Fibroblast Growth Factor 2 - pharmacology; Fibroblasts - drug effects; Fibroblasts - physiology; Flavonoids - pharmacology; Humans; In Situ Nick-End Labeling; Lactoferrin - metabolism; Lactoferrin - pharmacology; MAP Kinase Kinase Kinases - antagonists & inhibitors; Oryza - metabolism; Plants, Genetically Modified; Recombinant Proteins - pharmacology; Transforming Growth Factor beta1 - metabolism
• ISSN: 1067-1927; 1524-475X
• DOI: 10.1111/j.1524-475X.2009.00563.x

ABSTRACT 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.