title: Epithelial-mesenchymal status influences how cells deposit fibrillin microfibrils.
abstract: Here, we show that epithelial-mesenchymal status influences how cells deposit extracellular matrix. Retinal pigmented epithelial (RPE) cells that expressed high levels of E-cadherin and had cell-cell junctions rich in zona occludens (ZO)-1, β-catenin and heparan sulfate, required syndecan-4 but not fibronectin or protein kinase C α (PKCα) to assemble extracellular matrix (fibrillin microfibrils and perlecan). In contrast, RPE cells that strongly expressed mesenchymal smooth muscle α-actin but little ZO-1 or E-cadherin, required fibronectin (like fibroblasts) and PKCα, but not syndecan-4. Integrins α5β1 and/or α8β1 and actomyosin tension were common requirements for microfibril deposition, as was heparan sulfate biosynthesis. TGFβ, which stimulates epithelial-mesenchymal transition, altered gene expression and overcame the dependency on syndecan-4 for microfibril deposition in epithelial RPE cells, whereas blocking cadherin interactions disrupted microfibril deposition. Renal podocytes had a transitional phenotype with pericellular β-catenin but little ZO-1; they required syndecan-4 and fibronectin for efficient microfibril deposition. Thus, epithelial-mesenchymal status modulates microfibril deposition.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Baldwin
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Cain
authors.forename: Rachel
authors.initials: R
authors.lastname: Lennon
authors.forename: Alan
authors.initials: A
authors.lastname: Godwin
authors.forename: Catherine L R
authors.initials: CL
authors.lastname: Merry
authors.forename: Cay M
authors.initials: CM
authors.lastname: Kielty
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000205:Actomyosin / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure; D042361:Mammary Glands, Human / Q000378:metabolism / Q000648:ultrastructure; D020894:Microfibrils / Q000378:metabolism* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000648:ultrastructure; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D054392:Adipokines
chemical_list: D000199:Actins; D000205:Actomyosin; D015820:Cadherins; D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins; D006497:Heparan Sulfate; D016023:Integrins; D008840:Microfilament Proteins; D053671:Syndecan-4; D016212:Transforming Growth Factor beta; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; C541116:ACTA2 protein, human; C495270:CTNNB1 protein, human; C000605722:FBN1 protein, human; D054392:Adipokines; C508304:SDC4 protein, human; C569042:TJP1 protein, human
keywords: Cell–cell junction; Epithelial cell; Fibrillin-1; Fibronectin; Integrin; Mesenchymal cell; Perlecan; Syndecan