title: Discoidin domain receptor 2 regulates the adhesion of fibroblasts to 3D collagen matrices.
abstract: The collagen matrix constitutes the primary extracellular matrix (ECM) portion of mammalian connective tissues in which the interaction of the cell and the surrounding collagen fibers has a significant impact on cell and tissue physiology, including morphogenesis, development and motility. Discoidin domain receptors (DDR1 and DDR2) have been identified as the receptor tyrosine kinases that are activated upon collagen binding. However, there is a lack of evidence regarding the effect of DDRs on the mechanical interaction between fibroblasts and ECM. In this study, we demonstrated that one of the major phosphotyrosine proteins in human fibroblasts during 3D collagen matrix polymerization is DDR2. Treatment of fibroblasts in 3D collagen matrices with platelet-derived growth factor (PDFG) has been shown to increase DDR2 phosphorylation. Silencing of DDR2 with siRNA in fibroblasts significantly reduced the number of dendritic extensions regardless of whether cells were cultured in the collagen or fibronectin 3D matrices. Decreasing dendritic extensions in DDR2-silenced cells has also been shown to decrease the ability of fibroblast entanglement to collagen fibrils in 3D collagen matrices. Finally, we also showed that the silencing of DDR2 decreased the cell migration in 3D nested collagen matrices but had no effect on 3D floating matrix contraction. Collectively, these results suggest that DDR2 functioning is required for the membrane dynamics to control the mechanical attachment of fibroblasts to the 3D collagen matrices in an integrin-independent manner.
authors.affiliation: Department of Life Science (BK21 Program), Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Daehwan
authors.initials: D
authors.lastname: Kim
authors.forename: Eunae
authors.initials: E
authors.lastname: You
authors.forename: Na Young
authors.initials: NY
authors.lastname: Min
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Sangmyung
authors.initials: S
authors.lastname: Rhee
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D021982:Cell-Matrix Junctions / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*
chemical_list: D011975:Receptors, Mitogen; D019000:Phosphotyrosine; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases