caa a22 4500 445883480 CHVBK 20180317145552.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s10157-011-0479-0 doi (NATIONALLICENCE)springer-10.1007/s10157-011-0479-0 Dexamethasone increases the phosphorylation of nephrin in cultured podocytes [Elektronische Daten] [Teiko Ohashi, Keiko Uchida, Shinichi Uchida, Sei Sasaki, Kosaku Nitta] 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 24h 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 (30min) did not increase the phosphorylation, and actinomycinD 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 kinase1 (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. Japanese Society of Nephrology, 2011 Nephrin nationallicence Phosphorylation nationallicence Glucocorticoid nationallicence Podocyte nationallicence Ohashi Teiko Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, 162-8666, Tokyo, Japan aut Uchida Keiko Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, 162-8666, Tokyo, Japan aut Uchida Shinichi Department of Nephrology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, 113-8519, Tokyo, Japan aut Sasaki Sei Department of Nephrology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, 113-8519, Tokyo, Japan aut Nitta Kosaku Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, 162-8666, Tokyo, Japan aut Clinical and Experimental Nephrology Springer Japan 15/5(2011-10-01), 688-693 1342-1751 15:5<688 2011 15 10157 https://doi.org/10.1007/s10157-011-0479-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10157-011-0479-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ohashi Teiko Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, 162-8666, Tokyo, Japan aut NATIONALLICENCE 700 1- Uchida Keiko Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, 162-8666, Tokyo, Japan aut NATIONALLICENCE 700 1- Uchida Shinichi Department of Nephrology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Sasaki Sei Department of Nephrology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Nitta Kosaku Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, 162-8666, Tokyo, Japan aut NATIONALLICENCE 773 0- Clinical and Experimental Nephrology Springer Japan 15/5(2011-10-01), 688-693 1342-1751 15:5<688 2011 15 10157 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer