Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization

L. Tang, J. J. Wu, Q. Ma, T. Cui, F. M. Andreopoulos, J. Gil, J. Valdes, S. C. Davis, J. Li

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Background Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. Objectives To study the potential role of hLF in wound re-epithelialization. Materials and methods The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Results Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12-O-tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Conclusions Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing.

Original languageEnglish (US)
Pages (from-to)38-47
Number of pages10
JournalBritish Journal of Dermatology
Volume163
Issue number1
DOIs
StatePublished - Jul 1 2010

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Keywords

  • apoptosis
  • keratinocyte
  • migration
  • proliferation
  • re-epithelialization
  • recombinant human lactoferrin

ASJC Scopus subject areas

  • Dermatology

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