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, ?-catenin and heparan sulfate, required syndecan-4 but not fibronectin or protein kinase C ? (PKC?) to assemble extracellular matrix (fibrillin microfibrils and perlecan). In contrast, RPE cells that strongly expressed mesenchymal smooth muscle ?-actin but little ZO-1 or E-cadherin, required fibronectin (like fibroblasts) and PKC?, but not syndecan-4. Integrins ?5?1 and/or ?8?1 and actomyosin tension were common requirements for microfibril deposition, as was heparan sulfate biosynthesis. TGF?, 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 ?-catenin but little ZO-1; they required syndecan-4 and fibronectin for efficient microfibril deposition. Thus, epithelial-mesenchymal status modulates microfibril deposition.

SUBMITTER: Baldwin AK 

PROVIDER: S-EPMC3874785 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature