Kidney & blood pressure research · 2009
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.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Okazaki Akiko, Mori Yasukiyo, Nakata Midori, Kimura Taikou, Sonomura Kazuhiro, Sakoda Chikako, Matsuoka Eiko, Ishida Mami, Yamahara Hideki, Kishimoto Noriko, Nakagawa Hisako, Matsubara Hiroaki
Аннотация
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.
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.