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

Am J Physiol Renal Physiol. 2014 Sep 15;307(6):F708-17. doi: 10.1152/ajprenal.00625.2013. Epub 2014 Jul 23.

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.

Keywords: glomerular parietal epithelial cells; mammalian target of rapamycin; sestrin 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Down-Regulation
  • Doxorubicin
  • Epithelial Cells / metabolism
  • Hyaluronan Receptors / metabolism
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism*
  • Kidney Glomerulus / metabolism*
  • Male
  • Mice
  • Nuclear Proteins / metabolism*
  • Puromycin Aminonucleoside
  • RNA, Small Interfering
  • Rats
  • Rats, Inbred WKY
  • Rats, Wistar
  • Ribosomal Protein S6 / metabolism
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Hyaluronan Receptors
  • Nuclear Proteins
  • RNA, Small Interfering
  • Ribosomal Protein S6
  • Sesn2 protein, rat
  • Puromycin Aminonucleoside
  • Doxorubicin
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases