scholarly journals The Dysregulated Podocyte Phenotype

1999 ◽  
Vol 10 (1) ◽  
pp. 51-61 ◽  
Author(s):  
LAURA BARISONI ◽  
WILHELM KRIZ ◽  
PETER MUNDEL ◽  
VIVETTE D'AGATI
Keyword(s):  
Cell Proliferation ◽  
Minimal Change Disease ◽  
Human Kidney ◽  
Minimal Change ◽  
Ultrastructural Changes ◽  
Differentiation Markers ◽  
Ki 67 ◽  
Membranous Glomerulopathy ◽  
C3b Receptor ◽  
Collapsing Fsgs

Abstract. Podocytes are highly differentiated, postmitotic cells, whose function is largely based on their complex cytoarchitecture. The differentiation of podocytes coincides with progressive expression of maturity markers, including WT-1, CALLA, C3b receptor, GLEPP-1, podocalyxin, and synaptopodin. In collapsing forms of focal segmental glomerulosclerosis (FSGS), including idiopathic FSGS and HIV-associated nephropathy, podocytes undergo characteristic, irreversible ultrastructural changes. This study analyzes the expression pattern of the above differentiation markers and of the proliferation marker Ki-67 in collapsing idiopathic FSGS and HIV-associated nephropathy compared with minimal change disease, membranous glomerulopathy, as well as normal adult and fetal human kidney. In minimal change disease and membranous glomerulopathy, all mature podocyte markers were retained at normal levels despite severe proteinuria and foot process fusion; no cell proliferation was observed. In contrast, in collapsing idiopathic FSGS and HIV-associated nephropathy, there was disappearance of all markers from all collapsed glomeruli and of synaptopodin from 16% of noncollapsed glomeruli. This phenotypic dysregulation of podocytes was associated with cell proliferation in both diseases. It is concluded that the loss of specific podocyte markers defines a novel dysregulated podocyte phenotype and suggests a common pathomechanism in collapsing FSGS, whether idiopathic or HIV-associated.

Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome

1992 ◽  
Vol 82 (6) ◽  
pp. 641-650 ◽  
Author(s):  
Robert Zietse ◽  
Gerrit J. Wenting ◽  
Pieter Kramer ◽  
Maarten A. Schalekamp ◽  
Willem Weimar
Keyword(s):  
Glomerular Filtration Rate ◽  
Cyclosporin A ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Minimal Change Disease ◽  
Renal Plasma Flow ◽  
Minimal Change ◽  
Effective Renal Plasma Flow ◽  
Membranous Glomerulopathy ◽  
Glomerular Barrier

1. To elucidate the mechanisms by which cyclosporin A diminishes proteinuria, we studied 20 patients with severe nephrotic syndrome. Biopsy-established pathologies included minimal change disease (n = 5), membranous glomerulopathy (n = 6), membranoproliferative glomerulonephritis (n = 5) and focal segmental glomerulosclerosis (n = 4). Before, at the end of a 90 day course of cyclosporin A, and finally 1 month after stopping cyclosporin A we determined 24 h protein excretion. Measurements of glomerular filtration rate, effective renal plasma flow, fractional clearance rates of albumin and immunoglobulins with different charges and the transglomerular sieving of uncharged dextrans of broad size distribution were used to study the effects of cyclosporin A on renal perfusion and the glomerular filtration barrier. The findings were analysed with a theoretical model of solute transport. 2. Among the different forms of glomerulopathy the response to low-dose cyclosporin A (trough levels 32.0–36.9 ng/ml) varied markedly. In minimal change disease, proteinuria decreased from 9.5 ± 3.1 to 1.3 ± 0.2 g/24 h (mean ± sem, P < 0.01). This response was due to restoration of the charge selectivity of the glomerular barrier. The depressed value of the glomerular permeability coefficient also returned to normal. Glomerular filtration rate, effective renal plasma flow and renal vascular resistance did not change. Proteinuria returned after stopping cyclosporin A, although it did not reach pretreatment levels. In membranous glomerulopathy, proteinuria fell from 9.9 ± 1.5 to 1.8 ± 0.3 g/24 h (P < 0.01). Changes in protein excretion and dextran sieving were compatible with an increase in glomerular permselectivity and a decrease in filtrate flow through the ‘shunt’ pathway. Glomerular filtration rate was maintained, although effective renal plasma flow fell significantly. Proteinuria relapsed after stopping cyclosporin A. In membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis proteinuria did not respond to cyclosporin A, although cyclosporin A exerted important haemodynamic effects. 3. In minimal change disease and membranous glomerulopathy cyclosporin A exerts its beneficial effects on proteinuria through changes in the properties of the glomerular barrier, resulting in increased charge and size selectivity, respectively.

scholarly journals Molecular Mechanisms of Proteinuria in Minimal Change Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Shrey Purohit ◽  
Federica Piani ◽  
Flor A. Ordoñez ◽  
Carmen de Lucas-Collantes ◽  
Colin Bauer ◽  
...  
Keyword(s):  
T Cells ◽  
Minimal Change Disease ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Experimental Studies ◽  
Kidney Tissue ◽  
Disease Process ◽  
Minimal Change ◽  
Ultrastructural Changes ◽  
Genome Wide Association Studies

Minimal change disease (MCD) is the most common type of idiopathic nephrotic syndrome in childhood and represents about 15% cases in adults. It is characterized by massive proteinuria, edema, hypoalbuminemia, and podocyte foot process effacement on electron microscopy. Clinical and experimental studies have shown an association between MCD and immune dysregulation. Given the lack of inflammatory changes or immunocomplex deposits in the kidney tissue, MCD has been traditionally thought to be mediated by an unknown circulating factor(s), probably released by T cells that directly target podocytes leading to podocyte ultrastructural changes and proteinuria. Not surprisingly, research efforts have focused on the role of T cells and podocytes in the disease process. Nevertheless, the pathogenesis of the disease remains a mystery. More recently, B cells have been postulated as an important player in the disease either by activating T cells or by releasing circulating autoantibodies against podocyte targets. There are also few reports of endothelial injury in MCD, but whether glomerular endothelial cells play a role in the disease remains unexplored. Genome-wide association studies are providing insights into the genetic susceptibility to develop the disease and found a link between MCD and certain human haplotype antigen variants. Altogether, these findings emphasize the complex interplay between the immune system, glomerular cells, and the genome, raising the possibility of distinct underlying triggers and/or mechanisms of proteinuria among patients with MCD. The heterogeneity of the disease and the lack of good animal models of MCD remain major obstacles in the understanding of MCD. In this study, we will review the most relevant candidate mediators and mechanisms of proteinuria involved in MCD and the current models of MCD-like injury.

Expression of β-Catenin in Hepatocellular Carcinoma

2001 ◽  
Vol 71 (3) ◽  
pp. 116-125
Author(s):  
Norina Basa ◽  
Daniela Lazar ◽  
Remus Cornea ◽  
Sorina Taban ◽  
Melania Ardelean ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Mitotic Index ◽  
Histological Grade ◽  
Proliferation Index ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
B Virus ◽  
Development And Evolution

Alteration of β-catenin expression is involved in the development and evolution of hepatocellular carcinoma (HCC); β-catenin is able to influence tumor cell proliferation. We analyzed the immunohistochemical (IHC) expression of β-catenin on a group of 32 patients diagnosed with HCC using the anti-β-catenin monoclonal antibody (clone E247). We correlated the expression of β-catenin with the proliferation index of Ki-67 (PI Ki-67), the mitotic index (MI) and other clinical and pathological features. We observed an altered β-catenin expression in 58.38% of all HCC cases. This expression was insignificantly correlated with tumor size (]5 cm) (p = 0.683), histological grade G1-G2 (p = 0.307), vascular invasion (p = 0.299) and advanced pT stage (p = 0.453); we obtained a significantly higher MI in HCC with altered β-catenin expression (p = 0.018), as compared to HCC without overexpression (1.66 � 1.37) (p = 0.038) and a PI Ki-67 of 22.49 � 20.1 and 28.24 � 18.2, respectively in tumors with altered β-catenin expression with insignificant differences compared to HCC without overexpression (25.95 � 15.2) (p = 0.682 and p = 0.731, respectively). According to the results we obtained, aberrant β-catenin expression in HCC was correlated with a high mitotic index, therefore playing an important role in tumor progression by stimulating tumor cell proliferation; non-nuclear β-catenin overexpression can have a pathological significance in HCC, especially in cases of HCC associated with hepatitis B virus (HBV) infection.

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