English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Podocytes form unique cell-cell junctions (slit diaphragms) that are central to glomerular selectivity, although regulation and mechanisms of slit diaphragm assembly are poorly understood. With the use of cultured podocytes, a paracellular permeability flux assay was established to characterize properties of the size-selective barrier. Paracellular flux of differentiated podocytes was measured using anionic fluorescent dextrans of 3, 10, 40, and 70 kD. Podocytes form a highly selective barrier with a 160-fold difference in flux from the 3-kD dextran (11 pmol/min) to the 70-kD dextran (0.06 pmol/min). Barrier development was dependent on podocyte differentiation and not affected by dextran charge. Puromycin, a known podocyte toxin, increased flux 250% in a dose-dependent manner without affecting cell viability. Screening with modulators of specific signaling pathways identified reversible increases in flux with Src tyrosine and Rho kinase inhibition. The calcium switch model of epithelial junction assembly was modified to determine whether podocytes regulate barrier assembly. When cultured in low calcium for 90 min, flux increased by 300% and consistently returned to baseline 24 to 48 h after switching to normal calcium. Similar to classical epithelial junctions, barrier recovery occurred in the presence of cyclohexamide, an inhibitor of protein synthesis. During the calcium switch, there were reversible changes in localization and detergent solubility of the slit diaphragm protein ZO-1 and alpha-actinin-4, whereas nephrin and podocin solubility were unchanged. Taken together, these findings demonstrate that cultured podocytes develop a selective size barrier that is regulated by specific signaling pathways, and similar to classical epithelial junctions, podocytes demonstrate synchronized assembly of the barrier.

journal of the american society of nephrology

Cultured Podocytes Establish a Size-Selective Barrier Regulated by Specific Signaling Pathways and Demonstrate Synchronized Barrier Assembly in a Calcium Switch Model of Junction Formation