The immunoexpression of glomerular NF-κB in proteinuric patients with proliferative and non-proliferative glomerulopathies

Abstract

Recent studies suggest that NF-κB activation plays an essential role in the activation of mesangial cells and macrophages through the transcriptional induction of inflammatory mediators of glomerular inflammation and injury. The aim of the present study was to determine, using an image analysis system, glomerular immunoexpression of NF-κB (nuclear translocation of p65) in proteinuric patients with proliferative and non-proliferative glomerulopathies. Thirty-six proteinuric patients with idiopathic proliferative glomerulopathies (PG group) and 28 proteinuric participants with non-proliferative glomerulopathies (NPG group) were examined by percutaneous renal biopsy. As a control 12 biopsy specimens of the kidneys removed because of trauma were used. In the PG group the mean values of the glomerular immunoexpression of NF-κB were significantly increased as compared to both NPG patients and controls. In the PG but not in the MPG group glomerular immunoexpression of NF-κB was significantly positively correlated with the degree of proteinuria. Moreover, in the PG group glomerular immunoexpression of NF-κB was positively correlated with the mesangial cells, mesangial area and glomerular monocytes/macrophages. In conclusion, our results strongly suggest a role of NF-κB in glomerular injury in proteinuric patients with proliferative glomerulopathies.

Review of molecular biological research on the treatment of membranous nephropathy with Tripterygium glycosides based on TCM theory

“…[24] At the same time, Jilin Chen et al [25] conducted a retrospective cohort study and found that CXCL8 was highly correlated with the prognosis of MN;MMP9, MMP2 and TGFB1 are significantly expressed in patients with MN, which can be used as diagnostic markers of MN. MMP9 is significantly correlated with proteinuria, and MMP9 is significantly increased in patients with proteinuria in nephropathy [26,27] ; Studies have found that glomerular inflammation in MN lesions has different signaling pathways, and PTGS2 and monocytes/ macrophages are involved in the inflammatory process of nephritis [28] ;Tumor necrosis factor (TNF), a pleiotropic cytokine with proinflammatory and immunomodulatory properties, has an important role in renal disease, which predicts renal progression in patients with MN [29] ;Immunohistochemistry confirmed the high expression of VEGFA in MN renal biopsy specimens.…”

“…[ 24 ] At the same time, Jilin Chen et al [ 25 ] conducted a retrospective cohort study and found that CXCL8 was highly correlated with the prognosis of MN;MMP9, MMP2 and TGFB1 are significantly expressed in patients with MN, which can be used as diagnostic markers of MN. MMP9 is significantly correlated with proteinuria, and MMP9 is significantly increased in patients with proteinuria in nephropathy [ 26 , 27 ] ; Studies have found that glomerular inflammation in MN lesions has different signaling pathways, and PTGS2 and monocytes/macrophages are involved in the inflammatory process of nephritis [ 28 ] ;Tumor necrosis factor (TNF), a pleiotropic cytokine with proinflammatory and immunomodulatory properties, has an important role in renal disease, which predicts renal progression in patients with MN [ 29 ] ;Immunohistochemistry confirmed the high expression of VEGFA in MN renal biopsy specimens. VEGFA plays an important role in the pathogenesis of IMN through PI3K/AKT signaling pathway, providing a new target for the treatment of IMN [ 30 ] ;Researchers found that CXCL12 in serum and urine of MN patients was significantly increased, and podocyte proliferation was inhibited in vitro induced podocyte injury model, CXCL12/CXCR4 and phosphorylated STAT3 (p-STAT3) were increased, and CXCL12/CXCR4 and p-STAT3 promoted cell proliferation.…”

ABIN1 Determines Severity of Glomerulonephritis via Activation of Intrinsic Glomerular Inflammation

“…14,15 A similar study reported enhanced glomerular cell NF-kB activation in kidney biopsy specimens from different cohorts of patients with proliferative GN, including membranoproliferative GN, IgA nephropathy, and mesangial proliferative IgM GN. 52 Another group also found enhanced NF-kB activity in podocytes and other glomerular cells in biopsy specimens from patients with lupus nephritis and IgA nephropathy and patients with nonproliferative membranous nephropathy compared with healthy controls. 53 More direct evidence of podocyte activity was indicated in a study that found that podocyte-specific NEMOdeficient mice have faster recovery from anti-GBMe mediated glomerular injury.…”