Differential effects of hyaluronan and its fragments on fibroblasts: relation to wound healing.
Hyaluronan (HA) is involved in wound healing and its biological properties depend on its molecular size. The effects of native HA and HA-12 and HA-880 saccharide fragments on human fibroblast proliferation and expression of matrix-related genes were studied. The three HA forms promoted cell adhesion and proliferation. Matrix metalloproteinase-1 and -3 mRNA were increased by all HA forms, whereas only HA-12 stimulated the expression of the tissue inhibitor of metalloproteinase 1. HA-12 enhanced type I collagen and transforming growth factor-beta (TGF-beta) 1 expression. Interestingly, HA-12 and native HA stimulated type III collagen and TGF-beta3. HA and its fragments activated Akt and extracellular-regulated kinases 1/2 and p38. Inhibition of these signaling pathways suggested their implication in most of the effects. Only native HA activated nuclear factor-kappaB and activating protein 1. Use of CD44 siRNA suggests that this HA receptor is partly implicated in the effects, although it does not rule out the involvement of other receptors. Depending on its size, HA may exert differential regulation on the wound-healing process. Furthermore, the HA up-regulation of type III collagen and TGF-beta3 expression suggests that it may promote a fetal-like cell environment that favors scarless healing.
David-Raoudi
Maha
M
Laboratory of Connective Tissue Biochemistry, Faculty of medicine, Caen, France.
Tranchepain
Frédéric
F
Deschrevel
Brigitte
B
Vincent
Jean-Claude
JC
Bogdanowicz
Patrick
P
Boumediene
Karim
K
Pujol
Jean-Pierre
JP
D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D024042:Collagen Type I; D018960:Hyaluronan Receptors; D016328:NF-kappa B; D019715:Tissue Inhibitor of Metalloproteinase-1; D053782:Transforming Growth Factor beta3; D006820:Hyaluronic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1