title: Expression of a novel stress-inducible protein, sestrin 2, in rat glomerular parietal epithelial cells.
abstract: Sestrin 2, initially identified as a p53 target protein, accumulates in cells exposed to stress and inhibits mammalian target of rapamycin (mTOR) signaling. In normal rat kidneys, sestrin 2 was selectively expressed in parietal epithelial cells (PECs), identified by the marker protein gene product 9.5. In adriamycin nephropathy, sestrin 2 expression decreased in PECs on day 14, together with increased expression of phosphorylated S6 ribosomal protein (P-S6RP), a downstream target of mTOR. Sestrin 2 expression was markedly decreased on day 42, coinciding with glomerulosclerosis and severe periglomerular fibrosis. In puromycin aminonucleoside nephropathy, decreased sestrin 2 expression, increased P-S6RP expression, and periglomerular fibrosis were observed on day 9, when massive proteinuria developed. These changes were transient and nearly normalized by day 28. In crescentic glomerulonephritis, sestrin 2 expression was not detected in cellular crescents, whereas P-S6RP increased. In conditionally immortalized cultured PECs, the forced downregulation of sestrin 2 by short hairpin RNA resulted in increased expression of P-S6RP and increased apoptosis. These data suggest that sestrin 2 is involved in PEC homeostasis by regulating the activity of mTOR. In addition, sestrin 2 could be a novel marker of PECs, and decreased expression of sestrin 2 might be a marker of PEC injury.
authors: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan;
authors: Hiroko
authors: H
authors: Hamatani
authors: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan; hiromura@gunma-u.ac.jp.
authors: Keiju
authors: K
authors: Hiromura
authors: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan;
authors: Toru
authors: T
authors: Sakairi
authors: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan;
authors: Satoshi
authors: S
authors: Takahashi
authors: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan;
authors: Mitsuharu
authors: M
authors: Watanabe
authors: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan;
authors: Akito
authors: A
authors: Maeshima
authors: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan; and.
authors: Takamoto
authors: T
authors: Ohse
authors: Division of Nephrology, University of Washington, Seattle, Washington.
authors: Jeffery W
authors: JW
authors: Pippin
authors: Division of Nephrology, University of Washington, Seattle, Washington.
authors: Stuart J
authors: SJ
authors: Shankland
authors: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan;
authors: Yoshihisa
authors: Y
authors: Nojima
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D004317:Doxorubicin; D004847:Epithelial Cells / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011692:Puromycin Aminonucleoside; D034741:RNA, Small Interfering; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D038601:Ribosomal Protein S6 / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000084622:Sestrins
chemical_list: D004317:Doxorubicin; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; D011692:Puromycin Aminonucleoside; D034741:RNA, Small Interfering; D038601:Ribosomal Protein S6; D058570:TOR Serine-Threonine Kinases; C583887:Sesn2 protein, rat; D000084622:Sestrins; C546845:mTOR protein, rat
keywords: glomerular parietal epithelial cells; mammalian target of rapamycin; sestrin 2