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Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization

Tang, L. and Wu, J. J. and Ma, Q. and Cui, T. and Andreopoulos, F. M. and Gil, J. and Valdes, J. and Davis, S. C. and Li, J. (2010) Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization. British Journal of Dermatology, 163 (1). pp. 38-47. ISSN 0007-0963.

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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.

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Additional Information:© 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists. Accepted for publication 19 February 2010. This work was supported partially by NIH SBIR research grant R43 GM079025 (J.L.) and by funding from the Dermatology Foundation of South Florida (J.L.). We thank Mr Ramon Montero for his help in preparing lactoferrin hydrogel.
Funding AgencyGrant Number
NIHR43 GM079025
Dermatology Foundation of South FloridaUNSPECIFIED
Subject Keywords:apoptosis; keratinocyte; migration; proliferation; recombinant human lactoferrin; re-epithelialization
Issue or Number:1
Record Number:CaltechAUTHORS:20100713-111903236
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:19028
Deposited By: Tony Diaz
Deposited On:13 Jul 2010 20:30
Last Modified:03 Oct 2019 01:51

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