SPARC-thrombospondin-2-double-null mice exhibit enhanced cutaneous wound healing and increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges

Pauli A. Puolakkainen, Amy D. Bradshaw, Rolf A. Brekken, May J. Reed, Themis Kyriakides, Sarah E. Funk, Michel D. Gooden, Robert B. Vernon, Thomas N. Wight, Paul Bornstein, E. Helene Sage

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Secreted protein acidic and rich in cysteine (SPARC) and thrombospondin-2 (TSP-2) are structurally unrelated matricellular proteins that have important roles in cell-extracellular matrix (ECM) interactions and tissue repair. SPARC-null mice exhibit accelerated wound closure, and TSP-2-null mice show an overall enhancement in wound healing. To assess potential compensation of one protein for the other, we examined cutaneous wound healing and fibrovascular invasion of subcutaneous sponges in SPARC-TSP-2 (ST) double-null and wild-type (WT) mice. Epidermal closure of cutaneous wounds was found to occur significantly faster in ST-double-null mice, compared with WT animals: histological analysis of dermal wound repair revealed significantly more mature phases of healing at 1, 4, 7, 10, and 14 days after wounding, and electron microscopy showed disrupted ECM at 14 days in these mice. ST-double-null dermal fibroblasts displayed accelerated migration, relative to WT fibroblasts, in a wounding assay in vitro, as well as enhanced contraction of native collagen gels. Zymography indicated that fibroblasts from ST-double-null mice also produced higher levels of matrix metalloproteinase (MMP)-2. These data are consistent with the increased fibrovascular invasion of subcutaneous sponge implants seen in the double-null mice. The generally accelerated wound healing of ST-double-null mice reflects that described for the single-null animals. Importantly, the absence of both proteins results in elevated MMP-2 levels. SPARC and TSP-2 therefore perform similar functions in the regulation of cutaneous wound healing, but fine-tuning with respect to ECM production and remodeling could account for the enhanced response seen in ST-double-null mice.

Original languageEnglish (US)
Pages (from-to)571-581
Number of pages11
JournalJournal of Histochemistry and Cytochemistry
Volume53
Issue number5
DOIs
StatePublished - May 2005

Keywords

  • Angiogenesis
  • Collagen
  • Dermis
  • Epidermis
  • Extracellular matrix
  • Matricellular
  • SPARC
  • Thrombospondin
  • Wound healing

ASJC Scopus subject areas

  • Anatomy
  • Histology

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  • Cite this

    Puolakkainen, P. A., Bradshaw, A. D., Brekken, R. A., Reed, M. J., Kyriakides, T., Funk, S. E., Gooden, M. D., Vernon, R. B., Wight, T. N., Bornstein, P., & Sage, E. H. (2005). SPARC-thrombospondin-2-double-null mice exhibit enhanced cutaneous wound healing and increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges. Journal of Histochemistry and Cytochemistry, 53(5), 571-581. https://doi.org/10.1369/jhc.4A6425.2005