title: SPARC/SFN interaction, suppresses type I collagen in dermal fibroblasts.
abstract: 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.
authors.affiliation: Department of Surgery/Plastic Surgery, UBC, Vancouver British Columbia, Canada.
authors.forename: Claudia
authors.initials: C
authors.lastname: Chavez-Muñoz
authors.forename: Ryan
authors.initials: R
authors.lastname: Hartwell
authors.forename: Reza B
authors.initials: RB
authors.lastname: Jalili
authors.forename: Seyed Mehdi
authors.initials: SM
authors.lastname: Jafarnejad
authors.forename: Amy
authors.initials: A
authors.lastname: Lai
authors.forename: Layla
authors.initials: L
authors.lastname: Nabai
authors.forename: Abdi
authors.initials: A
authors.lastname: Ghaffari
authors.forename: Peymon
authors.initials: P
authors.lastname: Hojabrpour
authors.forename: Natalia
authors.initials: N
authors.lastname: Kanaan
authors.forename: Vincent
authors.initials: V
authors.lastname: Duronio
authors.forename: Emma
authors.initials: E
authors.lastname: Guns
authors.forename: Artem
authors.initials: A
authors.lastname: Cherkasov
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007231:Infant, Newborn; D015603:Keratinocytes / Q000378:metabolism; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012867:Skin / Q000166:cytology*
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D024042:Collagen Type I; D015676:Osteonectin; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human