Global deletion of Ankrd1 results in a wound-healing phenotype associated with dermal fibroblast dysfunction.

Samaras SE, Almodóvar-García K, Wu N, Yu F, Davidson JM
Am J Pathol. 2015 185 (1): 96-109

PMID: 25452119 · PMCID: PMC4278243 · DOI:10.1016/j.ajpath.2014.09.018

The expression of ankyrin repeat domain protein 1 (Ankrd1), a transcriptional cofactor and sarcomeric component, is strongly elevated by wounding and tissue injury. We developed a conditional Ankrd1(fl/fl) mouse, performed global deletion with Sox2-cre, and assessed the role of this protein in cutaneous wound healing. Although global deletion of Ankrd1 did not affect mouse viability or development, Ankrd1(-/-) mice had at least two significant wound-healing phenotypes: extensive necrosis of ischemic skin flaps, which was reversed by adenoviral expression of ANKRD1, and delayed excisional wound closure, which was characterized by decreased contraction and reduced granulation tissue thickness. Skin fibroblasts isolated from Ankrd1(-/-) mice did not spread or migrate on collagen- or fibronectin-coated surfaces as efficiently as fibroblasts isolated from Ankrd1(fl/fl) mice. More important, Ankrd1(-/-) fibroblasts failed to contract three-dimensional floating collagen gels. Reconstitution of ANKRD1 by adenoviral infection stimulated both collagen gel contraction and actin fiber organization. These in vitro data were consistent with in vivo wound closure studies, and suggest that ANKRD1 is important for the proper interaction of fibroblasts with a compliant collagenous matrix both in vitro and in vivo.

Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

MeSH Terms (30)

Adenoviridae Animals Cell Movement Collagen Crosses, Genetic Exons Female Fibroblasts Gels Gene Deletion Gene Expression Profiling Genotype Green Fluorescent Proteins Male MAP Kinase Signaling System Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Muscle Proteins Necrosis Nuclear Proteins Organ Size Phenotype Promoter Regions, Genetic Recombination, Genetic Repressor Proteins RNA Skin Wound Healing

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