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.
Markan
Suchita
S
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Kohli
Harbir Singh
HS
Joshi
Kusum
K
Minz
Ranjana Walker
RW
Sud
Kamal
K
Ahuja
Monika
M
Anand
Shashi
S
Khullar
Madhu
M
D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015432:Glomerulonephritis, Membranoproliferative; D015433:Glomerulonephritis, Membranous; D005923:Glomerulosclerosis, Focal Segmental; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D051437:Renal Insufficiency / Q000209:etiology; D051742:Transcription Factor CHOP / Q000032:analysis / Q000235:genetics*; D055815:Young Adult
C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051742:Transcription Factor CHOP