Amelogenin is phagocytized and induces changes in integrin configuration, gene expression and proliferation of cultured normal human dermal fibroblasts.
Fibroblasts are central in wound healing by expressing important mediators and producing and remodelling extracellular matrix (ECM) components. This study aimed at elucidating possible mechanisms of action of the ECM protein amelogenin on normal human dermal fibroblasts (NHDF). Amelogenin at 100 and 1000 microg/ml increased binding of NHDF via several integrins, including alphavbeta3, alphavbeta5 and alpha5beta1. Further, both surface interaction and cellular uptake of amelogenin by NHDF was observed using scanning and transmission electron microscopy. Gene microarray studies showed >8-fold up or down-regulation of genes, of which most are involved in cellular growth, migration and differentiation. The effect of amelogenin was exemplified by increased proliferation over 7 days. In conclusion, the beneficial effects of amelogenin on wound healing are possibly conducted by stimulating fibroblast signalling, proliferation and migration via integrin interactions. It is hypothesized that amelogenin stimulates wound healing by providing connective tissue cells with a temporary extracellular matrix.
Almqvist
Sofia
S
Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Box 412, 405 30, Göteborg, Sweden. sofia.almqvist@biomaterials.gu.se
Werthén
Maria
M
Johansson
Anna
A
Agren
Magnus S
MS
Thomsen
Peter
P
Lyngstadaas
S Petter
SP
D053523:Amelogenin / Q000737:chemistry*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008954:Models, Biological; D010587:Phagocytosis; D012867:Skin / Q000166:cytology*; D014945:Wound Healing
D053523:Amelogenin; D016023:Integrins