Stimulation of the follicular bulge LGR5+ and LGR6+ stem cells with the gut-derived human alpha defensin 5 results in decreased bacterial presence, enhanced wound healing, and hair growth from tissues devoid of adnexal structures.

Abstract

BACKGROUND:

Discovery of leucine-rich repeat-containing G-protein-coupled receptors 5 and 6 (LGR5 and LGR6) as markers of adult epithelial stem cells of the skin and intestine permits researchers to draw on the intrinsic cellular fundamentals of wound healing and proliferation dynamics of epithelial surfaces. In this study, the authors use the intestine-derived human alpha defensin 5 to stimulate epithelial proliferation, bacterial reduction, and hair production in burn wound beds to provide the field with initial insight on augmenting wound healing in tissues devoid of adnexal stem cells.

METHODS:

Murine third-degree burn wound beds were treated with (1) intestine-derived human alpha defensin 5, (2) skin-derived human beta defensin 1, and (3) sulfadiazine to determine their roles in wound healing, bacterial reduction, and hair growth.

RESULTS:

The human alpha defensin 5 peptide significantly enhanced wound healing and reduced basal bacterial load compared with human beta defensin 1 and sulfadiazine. Human alpha defensin 5 was the only therapy to induce LGR stem cell migration into the wound bed. In addition, gene heat mapping showed significant mRNA up-regulation of key wound healing and Wnt pathway transcripts such as Wnt1 and Wisp1. Ex vivo studies showed enhanced cell migration in human alpha defensin 5-treated wounds compared with controls.

CONCLUSIONS:

Application of human alpha defensin 5 increases LGR stem cell migration into wound beds, leading to enhanced healing, bacterial reduction, and hair production through the augmentation of key Wnt and wound healing transcripts. These findings can be used to derive gut protein-based therapeutics in wound healing.

• Authors: Denver Lough, Hui Dai, Mei Yang, Joel Reichensperger, Lisa Cox, Carrie Harrison, Michael W Neumeister
• Journal: Plastic and reconstructive surgery (Plast Reconstr Surg) Vol. 132 Issue 5 Pg. 1159-1171 (Nov 2013) ISSN: 1529-4242 [Electronic] United States
• PMID: 24165598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DEFA5 protein, human
• Intercellular Signaling Peptides and Proteins
• LGR5 protein, human
• LGR6 protein, human
• Receptors, G-Protein-Coupled
• alpha-Defensins

Topics

• Animals
• Burns (microbiology, pathology, physiopathology)
• Cell Movement
• Epithelial Cells (physiology)
• Hair (growth & development)
• Hair Follicle (physiopathology)
• Intercellular Signaling Peptides and Proteins (pharmacology)
• Intestines (cytology)
• Mice
• Receptors, G-Protein-Coupled (physiology)
• Skin (cytology)
• Stem Cells (physiology)
• Wnt Signaling Pathway (physiology)
• Wound Healing (physiology)
• alpha-Defensins (pharmacology)