Expression of a novel stress-inducible protein, sestrin 2, in rat glomerular parietal epithelial cells

被引:23
作者
Hamatani, Hiroko [1 ]
Hiromura, Keiju [1 ]
Sakairi, Toru [1 ]
Takahashi, Satoshi [1 ]
Watanabe, Mitsuharu [1 ]
Maeshima, Akito [1 ]
Ohse, Takamoto [2 ]
Pippin, Jeffery W. [3 ]
Shankland, Stuart J. [3 ]
Nojima, Yoshihisa [1 ]
机构
[1] Gunma Univ, Grad Sch Med, Dept Med & Clin Sci, Maebashi, Gunma 3718511, Japan
[2] Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Tokyo 113, Japan
[3] Univ Washington, Div Nephrol, Seattle, WA 98195 USA
关键词
sestrin; 2; glomerular parietal epithelial cells; mammalian target of rapamycin; DIABETIC-NEPHROPATHY; PODOCYTES; MTOR; ACTIVATION; INJURY; APOPTOSIS; KIDNEY; MICE; TOR;
D O I
10.1152/ajprenal.00625.2013
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:F708 / F717
页数:10
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