PMID- 15786734 OWN - NLM STAT- MEDLINE DCOM- 20050901 LR - 20190818 IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 269 IP - 1-2 DP - 2005 Jan TI - Interaction of keratinocytes and fibroblasts modulates the expression of matrix metalloproteinases-2 and -9 and their inhibitors. PG - 209-16 AB - Disruption of epidermal-mesenchymal communication due to a delay in epithelialization, increases the frequency of developing fibrotic conditions in skin. As matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) are two key enzymes involved in wound healing and tissue remodeling, here we examined the efficacy of keratinocyte-fibroblast interaction on modulation of these enzymes and their inhibitors. The conditioned media derived from keratinocytes and fibroblasts grown in upper and lower chambers of a co-culture system, respectively, were analyzed for MMP-2 and -9. Keratinocyte or fibroblast conditioned medium (FCM) was used as a control. Gelatinolytic activity analyzed by zymography showed that keratinocytes mainly express MMP-9 and to a lesser extent MMP-2; while fibroblasts express only MMP-2. In a co-culture system, the activities of both MMP-2 and MMP-9 markedly increased in conditioned media collected from bottom chambers. These findings were consistent with the level of MMP-2 and MMP-9 measured by Western blot. Using the same experimental setting, the levels of tissue inhibitors of MMPs (TIMPs) secreted by keratinocytes and fibroblasts grown in the same co-culture system were also evaluated. Western blot showed that fibroblasts secrete only TIMP-1 and TIMP-2 whose levels were increased by co-culturing fibroblasts with keratinocytes. In contrary the level of TIMP-3, which was mainly expressed by keratinocytes, increased by co-culturing these cells with fibroblasts. In conclusion, interaction of fibroblast-keratinocyte modulates the levels of MMP-2 and -9 and their inhibitors produced by these cells and this interaction may be critical for a better healing quality at a late stage of the wound healing process. FAU - Sawicki, Grzegorz AU - Sawicki G AD - Department of Pharmacology, Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada. FAU - Marcoux, Yvonne AU - Marcoux Y FAU - Sarkhosh, Kourosh AU - Sarkhosh K FAU - Tredget, Edward E AU - Tredget EE FAU - Ghahary, Aziz AU - Ghahary A LA - eng PT - Journal Article PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Culture Media, Conditioned) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - *Cell Communication MH - Cells, Cultured MH - Coculture Techniques MH - Culture Media, Conditioned MH - Fibroblasts/*enzymology MH - Humans MH - Keratinocytes/*enzymology MH - Matrix Metalloproteinase 2/analysis/*metabolism MH - Matrix Metalloproteinase 9/analysis/*metabolism MH - Tissue Inhibitor of Metalloproteinase-1/analysis/metabolism MH - Tissue Inhibitor of Metalloproteinase-2/analysis/metabolism MH - Wound Healing/physiology EDAT- 2005/03/25 09:00 MHDA- 2005/09/02 09:00 CRDT- 2005/03/25 09:00 PHST- 2005/03/25 09:00 [pubmed] PHST- 2005/09/02 09:00 [medline] PHST- 2005/03/25 09:00 [entrez] AID - 10.1007/s11010-005-3178-x [doi] PST - ppublish SO - Mol Cell Biochem. 2005 Jan;269(1-2):209-16. doi: 10.1007/s11010-005-3178-x.