Direct aldosterone action as a profibrotic factor via ROS-mediated SGK1 in peritoneal fibroblasts.

BACKGROUND/AIMS: Peritoneal fibrosis leads to discontinuation of peritoneal dialysis. Although aldosterone promotes tissue fibrosis in many organs, its contribution to peritoneal fibrosis and the underlying mechanism are poorly understood. The present study investigated the direct effect of aldosterone on cultured rat peritoneal fibroblasts (RPFs). METHODS: The expression of aldosterone synthase (CYP11B2), mineralocorticoid receptors (MRs), 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2), serum- and glucocorticoid-inducible protein kinase 1 (SGK1), and connective tissue growth factor (CTGF) mRNA was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). To determine the role of reactive oxygen species (ROS) induced by aldosterone, an active oxygen assay with several inhibitors was used. The ability of RPFs to produce aldosterone was examined by enzyme immunoassay. Small interfering RNA (siRNA) of SGK1 was transfected into cultured cells using lipofectamine. RESULTS: CYP11B2, MRs, and 11beta-HSD2 were expressed in RPFs. The release of aldosterone from RPFs into the culture medium was confirmed. Aldosterone increased the expression of SGK1 mRNA via ROS generation. Spironolactone, apocynin, and tempol significantly reduced SGK1 expression. Aldosterone upregulated CTGF transcripts significantly. SGK1 gene silencing suppressed aldosterone-induced CTGF expression. CONCLUSION: The local aldosterone system acts directly as a profibrotic factor via ROS-mediated SGK1 in RPFs.

Peritoneal mesothelial cells as a target of local aldosterone action: upregulation of connective tissue growth factor expression via serum- and glucocorticoid-inducible protein kinase 1.

BACKGROUND/AIMS: Peritoneal fibrosis can lead to the discontinuation of continuous ambulatory peritoneal dialysis. The present study investigated the direct effect of aldosterone, which influences tissue fibrosis, and its cellular mechanism using cultured rat peritoneal mesothelial cells (RPMCs). MATERIALS AND METHODS: The expression of aldosterone synthase (CYP11B2), mineralocorticoid receptors, 11beta-hydroxysteroid dehydrogenase 2, serum- and glucocorticoid-inducible protein kinase 1 (SGK1) and connective tissue growth factor (CTGF) was evaluated using reverse transcriptase-polymerase chain reaction and Western blot. The ability of RPMCs to produce aldosterone was examined by enzyme immunoassay. Small interfering RNA of SGK1 was transfected to determine the role of SGK1. RESULTS: CYP11B2, mineralocorticoid receptors and 11beta-hydroxysteroid dehydrogenase 2 were expressed in RPMCs. The release of aldosterone from RPMCs into the culture medium was confirmed. Stimulation of RPMCs with the addition of aldosterone significantly increased SGK1 expression and phosphorylation and CTGF upregulation, and these effects were completely inhibited by the mineralocorticoid receptor antagonist spironolactone. SGK1 gene silencing abrogated aldosterone-induced CTGF expression. CONCLUSION: The local aldosterone system exists and acts directly as a profibrotic factor in the peritoneal mesothelium.

[Hypercalcemia complicated with status nervosus in an elderly patient on hemodialysis during parental nutrition].

An 89-year-old male patient on hemodialysis presented clouding of consciousness caused by hypoglycemia during taking an anti-diabetic agent. His somnolent state continued in spite of glucose dispensation, and parental nutrition was started by a nasogastric tube because he couldn't have peroral ingestion. Though his blood glucose level recovered normal, his consciousness disorder was suspended, and he showed remarkable hypercalcemia. He was dosed with elcatonin, and the parental nutrient was changed to the other one that contained less vitamin D and calcium, and so his serum calcium level diminished slowly but he showed drowsiness about a month long. After resumption of peroral ingestion, his consciousness restored to the former condition rapidly. This case suggests that careful observation is needed in less active dialysis patients with parental nutrition because nutrient-contained vitamin D and calcium, which doesn't harm patients without renal insufficiency, may cause hypercalcemia.