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.
Keywords:
Cell–cell junction; Epithelial cell; Fibrillin-1; Fibronectin; Integrin; Mesenchymal cell; Perlecan; Syndecan.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / metabolism
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Actomyosin / genetics
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Actomyosin / metabolism
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Cadherins / genetics
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Cadherins / metabolism
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Cell Line
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Epithelial Cells / metabolism*
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Epithelial Cells / ultrastructure
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Epithelial-Mesenchymal Transition / genetics*
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Female
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Fibrillin-1
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Fibrillins
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Fibroblasts / metabolism
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Fibroblasts / ultrastructure
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Fibronectins / genetics
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Fibronectins / metabolism
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Gene Expression Regulation
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Heparitin Sulfate / metabolism
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Humans
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Integrins / genetics
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Integrins / metabolism
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Intercellular Junctions / metabolism
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Intercellular Junctions / ultrastructure
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Mammary Glands, Human / metabolism
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Mammary Glands, Human / ultrastructure
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Microfibrils / metabolism*
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Microfibrils / ultrastructure
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Microfilament Proteins / genetics*
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Microfilament Proteins / metabolism
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Organ Specificity
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Podocytes / metabolism
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Podocytes / ultrastructure
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Retinal Pigment Epithelium / metabolism
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Retinal Pigment Epithelium / ultrastructure
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Syndecan-4 / genetics
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Syndecan-4 / metabolism
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Transforming Growth Factor beta / pharmacology
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Zonula Occludens-1 Protein / genetics
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Zonula Occludens-1 Protein / metabolism
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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ACTA2 protein, human
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Actins
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CTNNB1 protein, human
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Cadherins
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FBN1 protein, human
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Fibrillin-1
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Fibrillins
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Fibronectins
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Integrins
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Microfilament Proteins
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SDC4 protein, human
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Syndecan-4
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TJP1 protein, human
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Transforming Growth Factor beta
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Zonula Occludens-1 Protein
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beta Catenin
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Actomyosin
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Heparitin Sulfate