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. Am J Physiol Renal Physiol. 2014 Jul 23; Authors: Hamatani H, Hiromura K, Sakairi T, Takahashi S, Watanabe M, Maeshima A, Ohse T, Pippin JW, Shankland SJ, Nojima Y 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 the PECs, identified by the marker PGP9.5. 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 shRNA resulted in increased expression of P-S6RP, and increased apoptosis. These data suggest that sestrin 2 is involved in PEC homeostasis b...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research