Serum And Glucocorticoid-inducible Kinase 1 Expression Research Articles

Going with the Wnt? Focus on “Hyperaldosteronism, hypervolemia, and increased blood pressure in mice expressing defective APC”

the wnt signaling system consists of ancient pathways with highly conserved core components tracing back more than 700 million years including insects and nematodes ([20][1]). Wnt signals classically play a crucial role in embryonic development concerning cell fate, motility, and polarity, as well

Downregulation of SGK1 by nucleotides in renal tubular epithelial cells

This study determined whether nucleotides that bind to purinergic receptors (P2R) regulate the expression or function of serum- and glucocorticoid-inducible kinase-1 (SGK1) in mouse renal inner medullar collecting duct cells (mIMCD-3). The SGK1 protein was detected by Western blotting. A significant reduction of cytosolic SGK1 expression was observed in the cells pretreated with P2R agonist adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), and the reduction could be reversed by P2R antagonists. This reduction was also observed in cells that were pretreated with agonists for P2R subtypes. Using ELISA, we observed a reduced SGK1 kinase activity in ATPgammaS-pretreated cells. This effect was reversed by P2R antagonists. Furthermore, an increase of SGK1 kinase activity in aldosterone-pretreated cells was suppressed by ATPgammaS. These studies demonstrate for the first time that SGK1 can be downregulated by nucleotides in renal collecting duct epithelial cells, likely via the activation of P2R, and suggest that activation of renal purinergic signaling regulates a SGK1-dependent pathway that is known to modulate ion transport in the renal collecting duct.

Enhanced Expression of Serum and Glucocorticoid-Inducible Kinase-1 in Kidneys of L-NAME-Treated Rats

Objective: The serum and glucocorticoid-inducible kinase-1 (SGK1) has previously been shown to be highly expressed in renal injury such as glomerulonephritis and diabetic nephropathy. Inhibition of nitric oxide synthase with N^G-nitro-L-arginine methyl ester (L-NAME) leads to arterial hypertension with subsequent renal injury. The present study explored whether chronic treatment with L-NAME affected renal SGK1 expression. Methods: 36 Sprague-Dawley rats were divided into a control group and an experimental group, in which hypertension was induced by oral administration of L-NAME (100 mg/kg/day). The rats were sacrificed 4 and 8 weeks, respectively, after initiation of the treatment. Blood pressure was determined with the tail-cuff method, urinary albumin and β₂-microglobulin concentration were measured using an immunoturbidimetric assay, and SGK1 expression in renal cortex was quantified by real-time PCR and Western blotting. Results: The administration of L-NAME increased systolic blood pressure significantly from 107 to 135 mm Hg within 4 weeks and to 155 mm Hg within 8 weeks. It further enhanced urinary excretion of albumin and β₂-microglobulin. Histology revealed marked fibrosis of glomerular and tubular tissue. The 4- and 8-week L-NAME treatment increased significantly (p < 0.01) SGK1 mRNA and protein abundance in renal cortex. Conclusions:L-NAME treatment leads to hypertension, proteinuria and renal fibrosis. It increases renal transcription and expression of SGK1, which has previously been shown to foster matrix protein deposition and could thus contribute to renal injury.