title: Mesangial proliferative nephritis in man is associated with increased expression of the cell survival factor, Bcl-2.
abstract: Although most studies suggest that the hypercellularity in mesangial proliferative nephritis is due to increased cell proliferation, we hypothesized that it may also be due to increased expression of survival factors that may block their removal (apoptosis). We therefore studied the expression of apoptosis preventing/delaying the bcl-2 gene product in the glomerulus with various human glomerulonephritides. Immunohistochemistry for Bcl-2, proliferating cell associated protein (Ki-67) and alpha-smooth muscle actin (alpha-SMA) was performed on 55 biopsied kidney tissues: 6 cases of orthostatic proteinuria as a control (OP); 6 cases of diffuse proliferative lupus nephritis (WHO type IV, LN-MPGN); 24 cases of IgA nephropathy (IgA); 9 cases of minimal change nephrosis and 10 cases of idiopathic membranous nephropathy. The number of Ki-67-positive cells and the expression of alpha-SMA in the glomerulus were significantly higher in LN-MPGN and IgA. There was a significant positive correlation between glomerular Bcl-2 expression and glomerular cell proliferation evaluated by the number of Ki-67-positive cells (r=0.605, p < 0.01) or glomerular alpha-SMA expression (r=0.674, p < 0.01). Glomerular expression of Bcl-2 in IgA or LN-MPGN was significantly higher than that in OP (p < 0.01 and p < 0.05 vs. OP, respectively). The Bcl-2-positive cells were present in mesangial locations and demonstrated a perinuclear pattern. These results suggest that maintenance of glomerular hypercellularity in human glomerular diseases is partly due to the prevention of mesangial cell death via Bcl-2 expression.
authors.affiliation: Department of Medicine, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Uda
authors.forename: A
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Y
authors.initials: Y
authors.lastname: Sugenoya
authors.forename: K
authors.initials: K
authors.lastname: Inui
authors.forename: T
authors.initials: T
authors.lastname: Taira
authors.forename: T
authors.initials: T
authors.lastname: Ideura
mesh_terms: D000199:Actins / Q000032:analysis / Q000096:biosynthesis; D017209:Apoptosis; D019254:Genes, bcl-2; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D000199:Actins; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2