SPARC/SFN interaction, suppresses type I collagen in dermal fibroblasts

J Cell Biochem. 2012 Aug;113(8):2622-32. doi: 10.1002/jcb.24137.


We previously suggested that keratinocyte releasable factors might modulate the wound healing process by regulating the expression of key extracellular matrix components such as collagenase (matrix metalloproteinase-1) and type I collagen in fibroblasts. The first one, we called it keratinocyte-derived anti-fibrogenic factor (KDAF), identified as stratifin (SFN) also named 14-3-3σ, revealing a strong collagenase activity. However, the second factor, which we named keratinocyte-derived collagen-inhibiting factor(s) (KD-CIF) that has shown to control the synthesis of type I collagen, was not known. Upon conducting a series of systematic protein purification methods followed by mass spectroscopy, two proteins: secreted protein acidic rich in cystein (SPARC) and SFN were identified in keratinocyte-conditioned media. Using co-immunoprecipitation and 3D modeling, we determined that SFN and SPARC form a complex thereby controlling the type I collagen synthesis and expression in fibroblasts. The levels of these proteins in fibrotic tissues (animal and human) were also evaluated and a differential expression of these proteins between normal and fibrotic tissue confirmed their potential role in development of fibrotic condition. In conclusion, this study describes for the first time an interaction between SPARC and SFN that may have implications for the regulation of matrix deposition and prevention of dermal fibrotic conditions such as hypertrophic scars and keloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / genetics
  • 14-3-3 Proteins / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism*
  • Exonucleases / genetics
  • Exonucleases / metabolism*
  • Exoribonucleases
  • Fibroblasts / metabolism*
  • Humans
  • Immunoprecipitation
  • Infant, Newborn
  • Keratinocytes / metabolism
  • Osteonectin / genetics
  • Osteonectin / metabolism*
  • Protein Binding
  • Skin / cytology*


  • 14-3-3 Proteins
  • Biomarkers, Tumor
  • Collagen Type I
  • Osteonectin
  • Exonucleases
  • Exoribonucleases
  • SFN protein, human