Effect of adenoviral mediated overexpression of fibromodulin on human dermal fibroblasts and scar formation in full-thickness incisional wounds

Alexander Stoff, Angel A. Rivera, J. Michael Mathis, Steven T. Moore, N. S. Banerjee, Maaike Everts, Antonio Espinosa-De-Los-Monteros, Zdenek Novak, Luis O. Vasconez, Thomas R. Broker, Dirk F. Richter, Dale Feldman, Gene P. Siegal, Mariam A. Stoff-Khalili, David T. Curiel

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Fibromodulin, a member of the small leucine-rich proteoglycan family, has been recently suggested as a biologically significant mediator of fetal scarless repair. To assess the role of fibromodulin in the tissue remodeling, we constructed an adenoviral vector expressing human fibromodulin cDNA. We evaluated the effect of adenovirus-mediated overexpression of fibromodulin in vitro on transforming growth factors and metalloproteinases in fibroblasts and in vivo on full-thickness incisional wounds in a rabbit model. In vitro, we found that Ad-Fibromodulin induced a decrease of expression of TGF-β1 and TGF-β2 precursor proteins, but an increase in expression of TGF-β3 precursor protein and TGF-β type II receptor. In addition, fibromodulin overexpression resulted in decreased MMP-1 and MMP-3 protein secretion but increased MMP-2, TIMP-1, and TIMP-2 secretion, whereas MMP-9 and MMP-13 were not influenced by fibromodulin overexpression. In vivo evaluation by histopathology and tensile strength demonstrated that Ad-Fibromodulin administration could ameliorate wound healing in incisional wounds. In conclusion, although the mechanism of scar formation in adult wounds remains incompletely understood, we found that fibromodulin overexpression improves wound healing in vivo, suggesting that fibromodulin may be a key mediator in reduced scarring.

Original languageEnglish
Pages (from-to)481-496
Number of pages16
JournalJournal of Molecular Medicine
Volume85
Issue number5
DOIs
StatePublished - 1 May 2007

Keywords

  • Adenovirus
  • Dermal fibroblasts
  • Fibromodulin
  • Matrix metalloproteinases
  • Scar formation
  • Tissue-derived inhibitors of matrix metalloproteinase
  • Transforming growth factor-β
  • Wound healing

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