Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 185, Issue 1, Pages 96-109Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2014.09.018
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases grant [DK065656-08]
- National Institute of General Medical Sciences [GM101947-02]
- National Institute of Arthritis and Skin and Musculoskeletal Diseases grant [AR056138]
- Department of Veterans Affairs
- Center for Stem Cell Biology
- Cancer Center [CA68485]
- Vanderbilt Diabetes Research and Training Center [DK20593]
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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 adenovirat 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(-/-) mice. More important, Ankrd1(-/-) fibroblasts failed to contract three-dimensional floating collagen gels. Reconstitution of ANKRD1 by adenovirat 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.
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