We show that epithelial-mesenchymal status influences how cells deposit extracellular matrix. Retinal pigmented epithelial (RPE) cells expressing high E-cadherin and with zona occludens (ZO)-1, β-catenin and heparan sulphate-rich cell-cell junctions, required syndecan-4 but not fibronectin or protein kinase C-α 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 protein kinase C-α, but not syndecan-4. Integrins α5/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 microfibril dependency on syndecan-4 by epithelial RPE cells, whilst blocking cadherin interactions disrupted microfibrils. 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.
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