title: Human corneal fibroblast migration and extracellular matrix synthesis during stromal repair: Role played by platelet-derived growth factor-BB, basic fibroblast growth factor, and transforming growth factor-β1.
abstract: The development of treatments that modulate corneal wound healing to avoid fibrosis during tissue repair is important for the restoration of corneal transparency after an injury. To date, few studies have studied the influence of growth factors (GFs) on human corneal fibroblast (HCF) expression of extracellular matrix (ECM) proteins such as collagen types I and III, proteoglycans such as perlecan, or proteins implicated in cellular migration such as α5β1-integrin and syndecan-4. Using in vitro HCFs, a mechanical wound model was developed to study the influence of the GFs basic fibroblast GF (bFGF), platelet-derived GF (PDGF-BB) and transforming GF-β1 (TGFβ1) on ECM protein production and cellular migration. Our results show that mechanical wounding provokes the autocrine release of bFGF and TGFβ1 at different time points during the wound closure. The HCF response to PDGF-BB was a rapid closure due to fast cellular migration associated with a high focal adhesion replacement and a high expression of collagen and proteoglycans, producing nonfibrotic healing. bFGF stimulated nonfibrotic ECM production and limited the migration process. Finally, TGFβ1 induced expression of the fibrotic markers collagen type III and α5β1 integrin, and it inhibited cellular migration due to the formation of focal adhesions with a low turnover rate. The novel in vitro HCF mechanical wound model can be used to understand the role played by GFs in human corneal repair. The model can also be used to test the effects of different treatments aimed at improving the healing process. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Departamento de Biología Celular, Histología y Farmacología. Facultad de Medicina. Grupo de Investigación Reconocido: Técnicas Ópticas para el Diagnóstico, Universidad de Valladolid, Valladolid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gallego-Muñoz
authors.affiliation: Departamento de Biología Celular, Histología y Farmacología. Facultad de Medicina. Grupo de Investigación Reconocido: Técnicas Ópticas para el Diagnóstico, Universidad de Valladolid, Valladolid, Spain.|Servicio de Oftalmología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Ibares-Frías
authors.affiliation: Servicio de Análisis Clínicos. Laboratorio de Genética, Hospital Universitario Rio Hortega de Valladolid, Valladolid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Garrote
authors.affiliation: Departamento de Estadística, Facultad de Ciencias, Universidad de Valladolid, Valladolid, Spain.
authors.forename: María Cruz
authors.initials: MC
authors.lastname: Valsero-Blanco
authors.affiliation: Departamento de Biología Celular, Histología y Farmacología. Facultad de Medicina. Grupo de Investigación Reconocido: Técnicas Ópticas para el Diagnóstico, Universidad de Valladolid, Valladolid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cantalapiedra-Rodríguez
authors.affiliation: Instituto Oftalmológico Fernández-Vega, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Merayo-Lloves
authors.affiliation: Departamento de Biología Celular, Histología y Farmacología. Facultad de Medicina. Grupo de Investigación Reconocido: Técnicas Ópticas para el Diagnóstico, Universidad de Valladolid, Valladolid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Carmen Martínez-García
mesh_terms: D000077214:Becaplermin / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003315:Cornea / Q000166:cytology*; D003470:Culture Media; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D003470:Culture Media; D019812:Heparan Sulfate Proteoglycans; D016023:Integrins; C490948:KERA protein, human; D021122:Protein Subunits; D011509:Proteoglycans; D012333:RNA, Messenger; C508304:SDC4 protein, human; D053671:Syndecan-4; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; C071927:perlecan; D000077214:Becaplermin
keywords: basic fibroblast growth factor; corneal stroma repair; extracellular matrix synthesis; human corneal fibroblasts; migration; platelet-derived growth factor-BB; transforming growth factor-β1