title: Syndecan-1 regulates cell migration and fibronectin fibril assembly.
abstract: Corneal scarring is a major cause of blindness worldwide and can result from the deposition of abnormal amounts of collagen fibers lacking the correct size and spacing required to produce a clear cornea. Collagen fiber formation requires a preformed fibronectin (FN) matrix. We demonstrate that the loss of syndecan1 (sdc1) in corneal stromal cells (CSC) impacts cell migration rates, the sizes and composition of focal and fibrillar adhesions, the activation of integrins, and the assembly of fibronectin into fibrils. Integrin and fibronectin expression are not altered on sdc1-null CSCs. Cell adhesion, spreading, and migration studies using low compared to high concentrations of FN and collagen I (CNI) or vitronectin (VN) with and without activation of integrins by manganese chloride show that the impact of sdc1 depletion on integrin activation varies depending on the integrin-mediated activity evaluated. Differences in FN fibrillogenesis and migration in sdc1-null CSCs are reversed by addition of manganese chloride but cell spreading differences remain. To determine if our findings on sdc1 were specific to the cornea, we compared the phenotypes of sdc1-null dermal fibroblasts with those of CSCs. We found that without sdc1, both cell types migrate faster; however, cell-type-specific differences in FN expression and its assembly into fibrils exist between these two cell types. Together, our data demonstrate that sdc1 functions to regulate integrin activity in multiple cell types. Loss of sdc1-mediated integrin function results in cell-type specific differences in matrix assembly. A better understanding of how different cell types regulate FN fibril formation via syndecans and integrins will lead to better treatments for scarring and fibrosis.
authors.affiliation: Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington DC 20037, USA. mastepp@gwu.edu
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Stepp
authors.forename: William P
authors.initials: WP
authors.lastname: Daley
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Bernstein
authors.forename: Sonali
authors.initials: S
authors.lastname: Pal-Ghosh
authors.forename: Gauri
authors.initials: G
authors.lastname: Tadvalkar
authors.forename: Alexey
authors.initials: A
authors.lastname: Shashurin
authors.forename: Sarah
authors.initials: S
authors.lastname: Palsen
authors.forename: Rosalyn A
authors.initials: RA
authors.lastname: Jurjus
authors.forename: Melinda
authors.initials: M
authors.lastname: Larsen
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology* / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D039001:Integrin alpha Chains / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D015636:Magnesium Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D053668:Syndecan-1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D039001:Integrin alpha Chains; D019012:Integrin beta1; D053668:Syndecan-1; D015636:Magnesium Chloride