Up regulation of the GRP-78 and GADD-153 and down regulation of Bcl-2 proteins in primary glomerular diseases: a possible involvement of the ER stress pathway in glomerulonephritis.

The role of endoplasmic reticulum (ER) stress in kidney diseases is not well elucidated. Fifty patients with primary glomerular diseases (PGD): minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN), and crescentic glomerulonephritis, n = 10 (each group) were enrolled. MCD, FSGS, and MGN patients were sub-grouped as nonproliferative glomerulonephritis (NPGN) and MPGN, RPGN as proliferative glomerulonephritis (PGN). Glucose regulated proteins (GRP-78), growth arrest and DNA damage inducible proteins (GADD-153), and Bcl-2 protein expression was analyzed by Western blotting, immunofluorescence and immunohistochemistry in the kidney biopsy. Up regulation of GADD-153, GRP-78, with more pronounced expression in PGN vs. NPGN (P < 0.05) and down regulation of Bcl-2 proteins was observed in the GN (PGD excluding MCD) as compared to MCD (P < 0.05). Our results suggest that renal injury in PGD is associated with ER stress and ER stress may be involved in the rapid progression of PGN to renal failure.