Altered tissue repair in hevin-null mice: inhibition of fibroblast migration by a matricellular SPARC homolog.
Matricellular proteins such as hevin, secreted protein acidic and rich in cysteine, and thrombospondin-2 play an important role during tissue repair through their influence on fundamental cellular activities such as adhesion, migration, proliferation, and extracellular matrix synthesis/reorganization. We have investigated the role played by hevin during excisional and incisional cutaneous wound repair in hevin-null mice. Hevin-null animals both close and heal their skin wounds faster than wild-type animals, as evidenced by enhanced macrophage infiltration of wound beds at early time points, the earlier appearance of mature extracellular matrix, and the overall higher maturity score. In addition, fibrovascular invasion of polyvinyl alcohol sponges was more robust in hevin-null mice, a result indicating that differences in cell migration might underlie the observed alterations in wound repair. Experiments in vitro showed that hevin induced the deadhesion and inhibited the migration of primary dermal fibroblasts in a Rac-1-dependent manner. These findings indicate that the differences in wound repair between hevin-null and wild-type animals can be attributed in part to the deadhesive function of hevin and reduced cell migration within dermal wound beds in which this protein is expressed.
Sullivan
Millicent M
MM
Department of Chemical Engineering, University of Delaware, Newark, Delaware 19716, USA. msullivan@udel.edu
Puolakkainen
Pauli A
PA
Barker
Thomas H
TH
Funk
Sarah E
SE
Sage
E Helene
EH
D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011142:Polyvinyl Alcohol; D012867:Skin / Q000166:cytology*; D015503:Surgical Sponges; D014945:Wound Healing / Q000502:physiology*
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; C503127:Sparcl1 protein, mouse; D011142:Polyvinyl Alcohol