No abstract available.
Hypertrophy* ; Interleukin-6* ; Podocytes*

Humans ; Podocytes ; physiology ; Proteinuria ; physiopathology

Diabetic nephropathy is one of the most common microvascular complications of diabetes mellitus. With an increasing prevalence, its proportion in end-stage renal diseases is ascending. Research on the mechanism of diabetic nephropathy was initially focused on the mesangial matrix and glomerular basement membrane. In recent years, changes in the structure and functions of glomerular filtration barriers, especially podocyte injury, has became new hotspots. Podocyte injury involves the decreases in the density and amount of podocytes, the hypertrophy and degeneration of podocytes, and foot-process effacement, along with changes in some specific protein structure and functions. It is the result of multiple factors and multiple pathways. This articles summarizes the common features of podocyte injury and its role in the development of diabetic nephropathy.
Diabetic Nephropathies ; pathology ; Humans ; Podocytes ; pathology

Humans ; Podocytes ; Receptors, Urokinase Plasminogen Activator

The development of the glomerular injury in diabetic nephropathy involves interactions between podocytes, endothelium, and the mesangium. Loss of podocytes is an early and critical step in the development of diabetic nephropathy, and analysis of structural lesions within the mesangium such as mesangiolysis implicate the loss of podocytes as a key mediating event. The BTBR ob/ob mouse has proved a useful tool to demonstrate that restoration of podocyte density, once thought to be an absolute barrier to glomerular repair, can be achieved with replacement of the hormone leptin that is constitutively absent in these mice. Restoration of podocyte density is associated with reversal of the structural lesions of morphologically advanced diabetic glomerular injury in this model. This finding, in conjunction with the demonstration in human diabetic patients with morphologically advanced diabetic nephropathy and with long-standing functioning pancreatic transplants of ten years duration that their diabetic nephropathy can be reversed, suggests that restoration of podocyte number and density is an appropriate target for the development of new therapeutics for diabetic nephropathy.
Animals ; Diabetic Nephropathies* ; Endothelium ; Humans ; Leptin ; Mice ; Negotiating ; Pathology* ; Podocytes

OBJECTIVE: To study the role of microRNA-17-5p (miR-17-5p) in the pathogenesis of pediatric nephrotic syndrome (NS) and its effect on renal podocyte apoptosis via the activin A (ActA)/Smads pathway. METHODS: An analysis was performed on 55 children with NS (NS group) who were admitted from March 2018 to March 2019. Fifty healthy children who underwent physical examination during the same period of time were enrolled as the control group. The mRNA expression of miR-17-5p in peripheral blood was measured and compared between the two groups. Human renal podocytes were transfected with antisense oligonucleotide recombinant plasmid containing miR-17-5p (inhibition group) or control vector containing nonsense random sequence (negative control group), and untreated human renal podocytes were used as the blank group. These groups were compared in terms of cell apoptosis and the mRNA and protein expression of miR-17-5p, ActA, and Smads after transfection. RESULTS: The NS group had a significantly higher level of miR-17-5p in peripheral blood than the control group (P<0.001). Compared with the blank and negative control groups, the inhibition group had significantly lower apoptosis rate and relative mRNA expression of miR-17-5p and significantly higher relative mRNA and protein expression of ActA, Smad2, and Smad3 (P<0.001). CONCLUSIONS There is an increase in the content of miR-17-5p in peripheral blood in children with NS. Low expression of miR-17-5p can inhibit the apoptosis of human renal podocytes, which may be associated with the upregulation of the mRNA and protein expression of ActA, Smad2 and Smad3.
Apoptosis ; Child ; Humans ; MicroRNAs ; genetics ; Nephrotic Syndrome ; genetics ; Podocytes ; Transfection

OBJECTIVE: To investigate the relationship between the expression of nephrin and the infiltration of macrophages in renal tissues in patients with lupus nephritis (LN), and to provide the evidence of potential mechanism of podocyte injury in LN. METHODS: In the study, 60 patients who were first diagnosed with LN by pathology were selected including 38 active LN patients with r-SLEDAI≥4, and another 10 patients of normal renal tissue were excised as a normal control group. The renal tissue and podocyte injury were observed through light and transmission electron microscope. The expression of nephrin and the infiltration of macrophages (CD68+cells) in the renal tissue of the 60 LN patients and 10 normal cases were detected by immunohistochemical and immunofluorescence method. Different statistical analysis methods were used to analyze the correlation between the variables. Variance analysis was used for comparison among the groups, while LSD test was used for comparison between every two groups. Pearson correlation analysis was used to analyze the correlation between the variables. RESULTS: (1)Of all the LN patients, 24 h urinary protein [(3.94±1.76) vs. (1.56±0.68), P<0.05], erythrocyte sedimentation rate (ESR) [(79.83±6.3) vs. (40.1±10.5), P<0.05] and serum creatinine [(106.58±14.9) vs. (79.1±9.89), P<0.05] were significantly increased in active group than those in inactive group, while C3 [(0.34±0.12) vs. (0.78±0.11), P<0.05], C4 [(0.07±0.04) vs. (0.17±0.10), P<0.05 ] and eGFR [(62.42±5.16) vs. (81.33±4.53), P<0.05] were significantly decreased in active group. (2)Compared with the normal control group, the expression of nephrin in renal tissue of the LN patients was significantly decreased, and the expression of nephrin in the active patients was significantly lower than that in inactive group (P<0.05). (3)Compared with the normal control group, the number of infiltrated macrophages in the LN patients was significantly increased, especially in the active patients (P<0.05). Macrophages were mainly found in glomeruli. (4)There was a significant negative correlation between the expression of nephrin and macrophage infiltration in renal tissues of the LN patients (r=0.761, P<0.001). CONCLUSION Macrophage infiltration in renal tissues may be one of the potential mechanisms of podocyte injury in lupus nephritis.
Humans ; Kidney ; Kidney Glomerulus ; Lupus Nephritis ; Macrophages ; Podocytes

OBJECTIVE: We propose a novel region- level self-supervised contrastive learning method USRegCon (ultrastructural region contrast) based on the semantic similarity of ultrastructures to improve the performance of the model for glomerular ultrastructure segmentation on electron microscope images. METHODS: USRegCon used a large amount of unlabeled data for pre- training of the model in 3 steps: (1) The model encoded and decoded the ultrastructural information in the image and adaptively divided the image into multiple regions based on the semantic similarity of the ultrastructures; (2) Based on the divided regions, the first-order grayscale region representations and deep semantic region representations of each region were extracted by region pooling operation; (3) For the first-order grayscale region representations, a grayscale loss function was proposed to minimize the grayscale difference within regions and maximize the difference between regions. For deep semantic region representations, a semantic loss function was introduced to maximize the similarity of positive region pairs and the difference of negative region pairs in the representation space. These two loss functions were jointly used for pre-training of the model. RESULTS: In the segmentation task for 3 ultrastructures of the glomerular filtration barrier based on the private dataset GlomEM, USRegCon achieved promising segmentation results for basement membrane, endothelial cells, and podocytes, with Dice coefficients of (85.69 ± 0.13)%, (74.59 ± 0.13)%, and (78.57 ± 0.16)%, respectively, demonstrating a good performance of the model superior to many existing image-level, pixel-level, and region-level self-supervised contrastive learning methods and close to the fully- supervised pre-training method based on the large- scale labeled dataset ImageNet. CONCLUSION USRegCon facilitates the model to learn beneficial region representations from large amounts of unlabeled data to overcome the scarcity of labeled data and improves the deep model performance for glomerular ultrastructure recognition and boundary segmentation.
Humans ; Electrons ; Endothelial Cells ; Learning ; Podocytes ; Kidney Diseases

Proteinuria is a characteristic finding in glomerular diseases and is closely associated with renal outcomes. In addition, therapeutic interventions that reduce proteinuria improve renal prognosis. Accumulating evidence has demonstrated that podocytes act as key modulators of glomerular injury and proteinuria. The podocyte, or glomerular visceral epithelial cell, is a highly specialized and differentiated cell that forms interdigitated foot processes with neighboring podocytes, which are bridged together by an extracellular structure known as the "slit diaphragm" (SD). The SD acts as a size- and charge-selective barrier to plasma protein. Derangement of SD structure or loss of SD-associated protein results in podocyte injury and proteinuria. During the past decades, several immune-modulating agents have been used for the treatment of glomerular diseases and for the reduction of proteinuria. Interestingly, recent studies have demonstrated that immunosuppressive agents can have a direct effect on the SD-associated proteins and stabilize actin cytoskeleton in podocyte and have therefore introduced the concept of nonimmunologic mechanism of renoprotection by immunomodulators. This review focuses on the evidence that immuno-modulating agents directly target podocytes.
Actin Cytoskeleton ; Epithelial Cells ; Foot ; Immunologic Factors ; Immunomodulation ; Immunosuppressive Agents* ; Nephrotic Syndrome ; Plasma ; Podocytes* ; Prognosis ; Proteinuria

Podocytopathy is glomerular lesions characterized by podocyte injury. It is observed in various glomerular diseases, but minimal change disease and focal segmental glomerulosclerosis (FSGS) are the prototypes. In this review, morphologic features of podocyte injury and subtypes of FSGS will be reviewed briefly. Effacement of podocyte foot processes is the most common feature of podocyte injury. As podocytic injury progresses, intracytoplasmic vacuoles, subpodocytic cyst, detachment of podocytes from the glomerular basement membrane and apoptosis develop. Glomerular capillary loops in epithelium-denuded area undergo capillary collapse. Synechia and hyalinosis may accompany this lesion. To manifest segmental sclerosis, podocyte loss above a threshold level may be required. Injured podocytes can injure neighboring intact podocytes, and thereby spread injury within the same lobule. FSGS can be categorized into five subtypes by morphologic characteristics; not otherwise specified (NOS), perihilar, cellular, tip, and collapsing types. Each subtype has been reported to show different clinical courses and associated conditions, but there are controversies on its significance. With recent progress in the discovery of genetic abnormalities causing FSGS and plasma permeability factors, we expect to unravel pathophysiology of FSGS and to understand histological sequences leading to FSGS in near future.
Apoptosis ; Capillaries ; Foot ; Glomerular Basement Membrane ; Glomerulosclerosis, Focal Segmental ; Nephrosis, Lipoid ; Permeability ; Plasma ; Podocytes ; Sclerosis ; Vacuoles