title: Dermatopontin interacts with fibronectin, promotes fibronectin fibril formation, and enhances cell adhesion.
abstract: We report that dermatopontin (DP), an abundant dermal extracellular matrix protein, is found in the fibrin clot and in the wound fluid, which comprise the provisional matrix at the initial stage of wound healing. DP was also found in the serum but at a lower concentration than that in wound fluid. DP co-localized with both fibrin and fibronectin on fibrin fibers and interacted with both proteins. Both normal fibroblast and HT1080 cell adhesion to the fibrin-fibronectin matrix were dose-dependently enhanced by DP, and the adhesion was mediated by α5β1 integrin. The cytoskeleton was more organized in the cells that adhered to the fibrin-fibronectin-DP complex. When incubated with DP, fibronectin formed an insoluble complex of fibronectin fibrils as visualized by electron microscopy. The interacting sites of fibronectin with DP were the first, thirteenth, and fourteenth type III repeats (III(1), III(13), and III(14)), with III(13) and III(14) assumed to be the major sites. The interaction between III(2-3) and III(12-14) was inhibited by DP, whereas the interaction between I(1-5) and III(12-14) was specifically and strongly enhanced by DP. Because the interaction between III(2-3) and III(12-14) is involved in forming a globular conformation of fibronectin, and that between I(1-5) and III(12-14) is required for forming fibronectin fibrils, DP promotes fibronectin fibril formation probably by changing the fibronectin conformation. These results suggest that DP has an accelerating role in fibroblast cell adhesion to the provisional matrix in the initial stage of wound healing.
authors.affiliation: Department of Plastic Surgery, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Kato
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.forename: Kazushi
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sumiyoshi
authors.forename: Noritaka
authors.initials: N
authors.lastname: Matsuo
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimada
authors.forename: Sakuhei
authors.initials: S
authors.lastname: Fujiwara
mesh_terms: D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism* / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation; D014945:Wound Healing / Q000187:drug effects
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C082019:DPT protein, human; D016326:Extracellular Matrix Proteins; D005353:Fibronectins