Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis

To date, studies of the role for epidermal integrin α3β1 in cutaneous wound re-epithelialization have produced conflicting results: wound studies in skin from global α3-null neonatal mice have implicated the integrin in promoting timely wound re-epithelialization, whereas studies in adult mice with...

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Main Authors: Sanjana Dhulipalla, Giesse Albeche Duarte, Lei Wu, Mathieu R. DiPersio, John M. Lamar, C. Michael DiPersio, Whitney M. Longmate
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:JID Innovations
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667026724000572
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Summary:To date, studies of the role for epidermal integrin α3β1 in cutaneous wound re-epithelialization have produced conflicting results: wound studies in skin from global α3-null neonatal mice have implicated the integrin in promoting timely wound re-epithelialization, whereas studies in adult mice with constitutive, epidermal-specific α3β1 deletion have not. The objective of this study was to utilize a model of inducible α3β1 deletion in the epidermis to clarify the role of α3β1 in the healing of adult wounds. We utilized the recently developed transgenic K14Cre-ERT::α3flx/flx mice (ie, inducible α3 epidermal knockout), permitting us to delete floxed Itga3 alleles (α3flx/flx) from epidermis just prior to wounding with topical treatment of 4-hydroxytamoxifen. This allows for the elucidation of α3β1-dependent wound healing in adult skin, free from compensatory mechanisms that may occur after embryonic deletion of epidermal α3β1 in the widely used constitutive α3β1-knockout mouse. We found that re-epithelializing wound gaps are larger in inducible α3 epidermal knockout mice than in control mice, indicating delayed healing, and that epidermal integrin α3β1 promotes healing of wounds, at least in part by enhancing keratinocyte proliferation. This work provides essential rationale for future studies to investigate integrin α3β1 as a therapeutic target to facilitate wound healing.
ISSN:2667-0267