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Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair.

Abstract
The matricellular protein periostin is expressed in the skin. Although periostin has been hypothesized to contribute to dermal homeostasis and repair, this has not been directly tested. To assess the contribution of periostin to dermal healing, 6 mm full-thickness excisional wounds were created in the skin of periostin-knockout and wild-type, sex-matched control mice. In wild-type mice, periostin was potently induced 5-7 days after wounding. In the absence of periostin, day 7 wounds showed a significant reduction in myofibroblasts, as visualized by expression of α-smooth muscle actin (α-SMA) within the granulation tissue. Delivery of recombinant human periostin by electrospun collagen scaffolds restored α-SMA expression. Isolated wild-type and knockout dermal fibroblasts did not differ in in vitro assays of adhesion or migration; however, in 3D culture, periostin-knockout fibroblasts showed a significantly reduced ability to contract a collagen matrix, and adopted a dendritic phenotype. Recombinant periostin restored the defects in cell morphology and matrix contraction displayed by periostin-deficient fibroblasts in a manner that was sensitive to a neutralizing anti-β1-integrin and to the FAK and Src inhibitor PP2. We propose that periostin promotes wound contraction by facilitating myofibroblast differentiation and contraction.
AuthorsChristopher G Elliott, Jian Wang, Xiaolei Guo, Shi-wen Xu, Mark Eastwood, Jianjun Guan, Andrew Leask, Simon J Conway, Douglas W Hamilton
JournalJournal of cell science (J Cell Sci) Vol. 125 Issue Pt 1 Pg. 121-32 (Jan 01 2012) ISSN: 1477-9137 [Electronic] England
PMID22266908 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • Cell Adhesion Molecules
  • Integrin beta1
  • Postn protein, mouse
  • Transforming Growth Factor beta
  • Collagen
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse
  • src-Family Kinases
Topics
  • Actins (metabolism)
  • Animals
  • Cell Adhesion Molecules (deficiency, genetics, metabolism)
  • Cell Differentiation
  • Cell Shape
  • Collagen (metabolism)
  • Focal Adhesion Kinase 1 (metabolism)
  • Granulation Tissue (metabolism)
  • Integrin beta1 (metabolism)
  • Kinetics
  • Mice
  • Mice, Knockout
  • Muscle, Smooth (metabolism)
  • Myofibroblasts (cytology, metabolism)
  • Signal Transduction
  • Skin (cytology, metabolism, pathology)
  • Transforming Growth Factor beta (metabolism)
  • Wound Healing
  • src-Family Kinases (metabolism)

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