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
| Autor: | Michael W. Neumeister, Denver Lough, Lisa Cox, Carrie Harrison, Mei Yang, Joel Reichensperger, Hui Dai |
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| Rok vydání: | 2013 |
| Předmět: |
alpha-Defensins
medicine.medical_specialty Alpha defensin Receptors G-Protein-Coupled Mice Cell Movement Internal medicine medicine Animals Wnt Signaling Pathway Skin Wound Healing integumentary system business.industry LGR6 Stem Cells LGR5 Wnt signaling pathway Epithelial Cells Cell migration Cell biology Intestines Endocrinology Intercellular Signaling Peptides and Proteins Surgery Stem cell Burns business Wound healing Hair Follicle Ex vivo Hair |
| Zdroj: | Plastic and Reconstructive Surgery. 132:1159-1171 |
| ISSN: | 0032-1052 |
| DOI: | 10.1097/prs.0b013e3182a48af6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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