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

Abstract

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.

Evidence for Activation of the Unfolded Protein Response in Collagen IV Nephropathies

“…Still, our data agree with previous studies depicting an increase in ER stress proteins in kidney biopsy specimens from patients with other nephropathies, such as diabetic nephropathy, 29 FSGS, and membranous nephropathy. 30,31 UPR Phenotype in a Mouse Carrying the Col4A3-G1332E Mutation Our data demonstrated (for the first time, to our knowledge), UPR activation in a relevant in vivo mouse model, the knockin Col4a3-G1332E mouse. These mice developed severe AS-like GBM pathology as early as at 3 months of age, based on electron microscopy of renal biopsy specimens.…”

Endoplasmic Reticulum: The Master Regulator of Stress Responses in Glomerular Diseases

“…Given that oxidative stress is also induced in anti-Thy1 nephritis rats, mesangial cell damage may be orchestrated by the link between ER stress and oxidative stress as pathogenic mediators. This evidence from a rat disease model might be consistent with evidence that ER stress estimated by GRP78 and CHOP expression is higher in patients with proliferative glomerulonephritis than in those with other glomerular diseases (Markan et al, 2009). Various pathogenic factors trigger ER stress in podocytes.…”

Participation of endoplasmic reticulum stress in the pathogenesis of spontaneous glomerulosclerosis–Role of intra-renal angiotensin system

“…17 Moreover, markers of ER stress have been identified in the renal biopsy specimens from patients with various inflammatory and noninflammatory glomerulopathies. 18,19 These studies, among others, point to the roles of ER stress in the pathophysiology of kidney disease.…”