A rice-derived recombinant human lactoferrin stimulates fibroblast proliferation, migration, and sustains cell survival.
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-beta1 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.
Tang
Ling
L
Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Cui
Tengjiao
T
Wu
James J
JJ
Liu-Mares
Wen
W
Huang
Ning
N
Li
Jie
J
D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007781:Lactoferrin / Q000378:metabolism / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D012275:Oryza / Q000378:metabolism*; D030821:Plants, Genetically Modified; D011994:Recombinant Proteins / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D005419:Flavonoids; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D020930:MAP Kinase Kinase Kinases; D007781:Lactoferrin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one