4.2 Article

Dexamethasone increases the phosphorylation of nephrin in cultured podocytes

Journal

CLINICAL AND EXPERIMENTAL NEPHROLOGY
Volume 15, Issue 5, Pages 688-693

Publisher

SPRINGER
DOI: 10.1007/s10157-011-0479-0

Keywords

Nephrin; Phosphorylation; Glucocorticoid; Podocyte

Funding

  1. Grants-in-Aid for Scientific Research [20249047, 22249032] Funding Source: KAKEN

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Background We reported that nephrin is phosphorylated at Y1204 and Y1228 under normal conditions and that the phosphorylation is decreased in puromycin nephrosis and in human minimal change nephrosis. These results indicate that the phosphorylation of nephrin is important for maintaining normal podocyte function. However, little is known about the regulation of nephrin phosphorylation. Here, we investigated whether glucocorticoid, a drug used to treat glomerular diseases with proteinuria, might affect the phosphorylation of nephrin. Methods Human cultured podocytes transiently expressing human nephrin were treated with dexamethasone (Dex), and the phosphorylation of nephrin was determined by immunoblot with the anti-pY1228 antibody. Results Dex treatment for 24 h increased the phosphorylation of nephrin; this increased phosphorylation was inhibited by the glucocorticoid receptor antagonist but not by the mineral corticoid receptor antagonist. A shorter incubation time (30 min) did not increase the phosphorylation, and actinomycin D and cycloheximide treatments abolished the increased phosphorylation. The activation of Src-family kinases was correlated with nephrin phosphorylation, both of which were abolished by small interfering RNA (siRNA) treatment for serum/glucocorticoid-induced kinase 1 (SGK1). Conclusions These results clarify a novel action of glucocorticoid on nephrin phosphorylation through SGK1. Glucocorticoid treatment for human glomerulonephritis may exert its function by regulating the phosphorylation of nephrin.

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