title: The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue.
abstract: BACKGROUND
  During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF), is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM) is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules.
  
  
  RESULTS
  Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration.
  
  
  CONCLUSIONS
  These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California, USA. feugate@citrus.ucr.edu
authors.forename: Jo Ellen
authors.initials: JE
authors.lastname: Feugate
authors.forename: Lina
authors.initials: L
authors.lastname: Wong
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
authors.forename: Manuela
authors.initials: M
authors.lastname: Martins-Green
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D030161:Avian Proteins; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000494:pharmacology / Q000502:physiology*; D002642:Chick Embryo; D024042:Collagen Type I / Q000096:biosynthesis; D024043:Collagen Type II / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005353:Fibronectins / Q000096:biosynthesis; D006097:Granulation Tissue / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D019063:Tenascin / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents; D030161:Avian Proteins; D019743:Chemokines, CXC; D024042:Collagen Type I; D024043:Collagen Type II; D016207:Cytokines; C071280:EMF-1 protein, Gallus gallus; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016209:Interleukin-8; D010455:Peptides; D019063:Tenascin