title: Functional peptide of dermatopontin produces fibrinogen fibrils and modifies its biological activity.
abstract: BACKGROUND
  Dermatopontin (DP), a small extracellular matrix protein, interacts with both fibrinogen and fibrin. DP accelerates fibrin fibril formation and enhances cell adhesion to fibrin fibrils but DP does not influence fibrinogen fibril formation. We have previously demonstrated that DP-4 (PHGQVVVAVRS) is a functional dermatopontin peptide (Wu et al., 2014).
  
  
  OBJECTIVE
  Identification of biological functions of DP-4.
  
  
  METHODS
  Protein-protein interactions were examined by solid-phase assay. The kinetics of fibrinogen/fibrin polymer formation was monitored by turbidity change, SDS-PAGE, and electron microscopy. A cell adhesion assay was performed using human umbilical vein endothelial cells.
  
  
  RESULTS
  Although DP promoted fibrin formation, the DP-4 peptide promoted fibrinogen polymerization but did not apparently affect fibrin formation. The polymerized fibrinogen formed straight solid fibrils comparable to the normally formed fibrin fibrils. A minimum functional sequence of the DP-4 peptide was determined to be VVVAVRS. An αC domain in fibrinogen was involved in the fibril formation. Fibrinogen fibrils made by DP-4 enhanced endothelial cell adhesion and spreading in a dose-dependent manner. This cell adhesion was inhibited by heparin and by anti-αvβ3 and β1 integrin antibodies.
  
  
  CONCLUSIONS
  DP-4 did not reproduce the full functional biological activities of DP with fibrin but DP-4 did promote fibrinogen fibril formation. The fibrinogen fibrils produced by DP-4 are useful as a novel synthetic biomaterial for therapeutic applications.
authors.affiliation: Department of Plastic Surgery, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593, Japan.
authors.forename: Weimin
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593, Japan. Electronic address: ookamoto@oita-u.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.affiliation: Department of Plastic Surgery, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Kato
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Matsuo
authors.affiliation: Laboratory of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kumai
authors.affiliation: Laboratory of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
authors.affiliation: Department of Dermatology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593, Japan.
authors.forename: Sakuhei
authors.initials: S
authors.lastname: Fujiwara
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry*; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D025941:Protein Interaction Mapping; D019030:Receptors, Vitronectin / Q000378:metabolism; D053667:Syndecans / Q000378:metabolism
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C082019:DPT protein, human; D016326:Extracellular Matrix Proteins; D039302:Integrin alphaVbeta3; D010455:Peptides; D019030:Receptors, Vitronectin; D053667:Syndecans; C094340:integrin alphavbeta1; D005337:Fibrin; D005340:Fibrinogen
keywords: DP-4 peptide; Dermatopontin; Fibrinogen; Fibrinogen fibril; Wound healing