Expression of a novel stress-inducible protein, sestrin 2, in rat glomerular parietal epithelial cells
Expression of a novel stress-inducible protein, sestrin 2, in rat glomerular parietal epithelial cells
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DOI：
10.1152/ajprenal.00625.2013
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发表时间：
2014-09-15
影响因子：
4.2
通讯作者：
Nojima, Yoshihisa
中科院分区：
文献类型：
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作者：
Hamatani, Hiroko;Hiromura, Keiju;Nojima, Yoshihisa
Sestrin 2最初被确定为p53的靶蛋白，在暴露于应激的细胞中积累并抑制哺乳动物雷帕霉素靶蛋白（mTOR）信号传导。在正常大鼠肾脏中，sestrin 2在壁上皮细胞（PECs）中选择性表达，由标记蛋白基因产物9.5鉴定。在阿霉素肾病中，第14天PECs中sestrin 2表达下降，同时mTOR下游靶点磷酸化S6核糖体蛋白（P-S6RP）表达增加。Sestrin 2表达在第42天明显降低，与肾小球硬化和严重肾小球周围纤维化同时发生。嘌呤霉素氨基核苷肾病患者在第9天出现大量蛋白尿时，观察到sestrin 2表达降低，P-S6RP表达升高，肾小球周围纤维化。这些变化是短暂的，到第28天几乎恢复正常。在月牙状肾小球肾炎中，月牙细胞中未检测到sestrin 2的表达，而P-S6RP则升高。在条件永生化培养的PECs中，短发夹RNA强制下调sestrin 2导致P-S6RP表达增加，细胞凋亡增加。这些数据表明，sestrin 2通过调节mTOR的活性参与PEC的内稳态。此外，sestrin 2可能是PEC的一个新的标志物，其表达降低可能是PEC损伤的一个标志。
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.