title: Suppression of cell adhesion through specific integrin crosstalk on mixed peptide-polysaccharide matrices.
abstract: Crosstalk of different integrins, which bind to distinct types of extracellular matrix proteins, promotes specific functions. This crosstalk has not been investigated in depth. Previously, we demonstrated that integrin-syndecan crosstalk accelerated cell adhesion. Here, we evaluated the crosstalk of two different integrins using mixed peptide-polysaccharide (chitosan or alginate) matrices. Two different integrin binding peptides, FIB1 (integrin αvβ3), EF1zz (integrin α2β1), and 531 (integrin α3β1), were mixed in various molar ratios (9:1, 4:1, 1:1) and conjugated on a polysaccharide matrix. The mixture of FIB1/EF1zz- and FIB1/531-polysaccharide matrices did not show any difference in human dermal fibroblast (HDF) adhesion against the mono polysaccharide matrices. Interestingly, the EF1zz/531-polysaccharide matrix (molar ratio = 1:4) exhibited significantly decreased cell adhesion, but other EF1zz/531-polysaccharide matrices did not show any difference. When we examined the signal transduction of the EF1zz/531(1:4), Y397 phosphorylation of FAK significantly decreased but Y514 phosphorylation of Src did not exhibit any differences. Further investigation revealed that this suppression was mediated by PI3K signaling through the activation of integrin, and PKA signaling modulated suppression of HDF attachment. These findings suggest that a mixed peptide-polysaccharide matrix using receptor specific ligands can regulate cellular functions through receptor-specific crosstalk and is a useful approach to understand receptor specific crosstalk.
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: hozumi@toyaku.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hozumi
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Fujimori
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kikkawa
authors.affiliation: Department 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
mesh_terms: D000595:Amino Acid Sequence; D019138:Antibodies, Blocking / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D016023:Integrins; D010455:Peptides; D011134:Polysaccharides; D048271:Chitosan; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases
keywords: Cell adhesion; Crosstalk; ECM (extracellular matrix); Integrin; Peptide; Polysaccharide