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Eleonora Veglia, Alessandro Pini, Aldo Moggio, Cristina Grange, Federica Premoselli, Gianluca Miglio, Katerina Tiligada, Roberto Fantozzi, Paul L Chazot, Arianna Carolina Rosa
Histamine has been reported to decrease the ultrafiltration coefficient, which inversely correlates with glomerular permselectivity, however the mechanism(s) underling this effect have never been investigated. This study aimed to assess whether histamine could exert a direct detrimental effect on podocyte permeability and the possible involvement of two key proteins for the glomerular slit diaphragm (SD) integrity, zonula occludens-1 (ZO-1) and P-cadherin. The effect of histamine (100 pM-1000nM) on coloured podocytes junctional integrity was evaluated functionally by a transwell assay of monolayer permeability and morphologically by electron microscopy...
October 14, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Jia Guo, Lili Yang, Yingjin Qiao, Zhangsuo Liu
Epithelial-mesenchymal transition (EMT) is important for diabetic nephropathy (DN). Podocytes are specialized epithelial cells, which form a major component of the glomerular filtration barrier. Podocyte damage has been suggested to be the primary mechanism behind the albuminuria associated with DN. The present study aimed to determine the function of glycogen synthase kinase (GSK)‑3β in EMT and barrier dysfunction of mouse podocytes exposed to high glucose (HG) conditions. Matured and differentiated podocytes were treated with normal glucose (NG), HG or NG + mannitol...
September 26, 2016: Molecular Medicine Reports
Rutger J Maas, Jeroen K Deegens, Bart Smeets, Marcus J Moeller, Jack F Wetzels
Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the key histological findings in patients with idiopathic nephrotic syndrome (INS). Although MCD and idiopathic FSGS are often considered to represent separate entities based on differences in their presenting characteristics, histology and outcomes, little evidence exists for this separation. We propose that MCD and idiopathic FSGS are different manifestations of the same progressive disease. The gradual development of FSGS in patients with non-remitting or relapsing INS has been well documented...
October 17, 2016: Nature Reviews. Nephrology
Ferruh Artunc, Erwin Schleicher, Cora Weigert, Andreas Fritsche, Norbert Stefan, Hans-Ulrich Häring
Insulin resistance is a systemic disorder that affects many organs and insulin-regulated pathways. The disorder is characterized by a reduced action of insulin despite increased insulin concentrations (hyperinsulinaemia). The effects of insulin on the kidney and vasculature differ in part from the effects on classical insulin target organs. Insulin causes vasodilation by enhancing endothelial nitric oxide production through activation of the phosphatidylinositol 3-kinase pathway. In insulin-resistant states, this pathway is impaired and the mitogen-activated protein kinase pathway stimulates vasoconstriction...
October 17, 2016: Nature Reviews. Nephrology
Songhui Zhai, Lijuan Hu, Lin Zhong, Yannan Guo, Liqun Dong, Ruizhen Jia, Zheng Wang
The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV) and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs), serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC) activation state were examined...
2016: Frontiers in Cellular and Infection Microbiology
Beom Jin Lim, Jae Won Yang, Woo Sung Do, Agnes B Fogo
Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS...
October 16, 2016: Journal of Pathology and Translational Medicine
Mukesh Madhukar Shete
Hypertension is one of the most common conditions seen in primary care and a major public health problem in India. It can lead to various complications if not detected early and treated appropriately. As per the latest Eighth Joint National Committee (JNC 8) the goal BP in most hypertensive patients age <60 years should be <140/90 mmHg and treatment can be started by selecting drugs from among 4 specific medication classes i.e. angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), calcium channel blocker (CCB) or diuretics...
April 2016: Journal of the Association of Physicians of India
Hideki Yokoi, Masashi Mukoyama
Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis. Transforming growth factor-β (TGF-β) is postulated to play a central role in the development of both fibrotic processes. Extracellular matrix proteins, particularly type I collagen and fibronectin, accumulate in the tissue during renal fibrogenesis. CCN2, also known as connective tissue growth factor (CTGF), is increased in the setting of fibrosis and modulates a number of downstream signaling pathways involved in the fibrogenic properties of TGF-β...
2017: Methods in Molecular Biology
Oleg Palygin, Daria V Ilatovskaya, Alexander Staruschenko
Protease-activated receptors (PARs) are a well-known family of transmembrane G-protein-coupled receptors (GPCRs). To date, four PARs have been identified and PAR1 and PAR2 are the most abundant receptors, which were shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligands that can be unmasked by serine protease cleavage. PARs are activated by endogenous serine proteases, such as thrombin (acts on PARs 1, 3 and 4) and trypsin (PAR2). PARs can be involved in glomerular, microvascular and inflammatory regulation of renal function in both normal and pathological conditions...
October 12, 2016: American Journal of Physiology. Renal Physiology
H Trimarchi, R Canzonieri, A Schiel, C Costales-Collaguazo, J Politei, A Stern, M Paulero, T Rengel, J Andrews, M Forrester, M Lombi, V Pomeranz, R Iriarte, A Muryan, E Zotta, M D Sanchez-Niño, A Ortiz
BACKGROUND: Certain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT). METHODS: Cross-sectional study including 65 individuals: controls (n = 20) and Fabry patients (n = 45, 23 of them not on ERT and 22 on ERT). Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia...
October 13, 2016: Journal of Translational Medicine
Michael J Randles, Sophie Collinson, Tobias Starborg, Aleksandr Mironov, Mira Krendel, Eva Königshausen, Lorenz Sellin, Ian S D Roberts, Karl E Kadler, Jeffrey H Miner, Rachel Lennon
Glomeruli are highly sophisticated filters and glomerular disease is the leading cause of kidney failure. Morphological change in glomerular podocytes and the underlying basement membrane are frequently observed in disease, irrespective of the underlying molecular etiology. Standard electron microscopy techniques have enabled the identification and classification of glomerular diseases based on two-dimensional information, however complex three-dimensional ultrastructural relationships between cells and their extracellular matrix cannot be easily resolved with this approach...
October 11, 2016: Scientific Reports
Chang-Yien Chan, Kar-Hui Ng, Jinmiao Chen, Jinhua Lu, Caroline Guat-Lay Lee, Puay-Hoon Tan, Stanley C Jordan, He Henry Yang, Hui-Kim Yap
Our established interleukin-13 ( IL-13 ) overexpression rat model of minimal change-like nephropathy provided a platform to study the molecular signalling pathways in T-helper 2 (Th2) cytokine associated minimal change nephrotic syndrome. We hypothesized that IL-13 may act directly on podocytes, causing podocyte foot process effacement and hence proteinuria in our rat model of minimal change-like nephropathy. This study aimed firstly to delineate the glomerular "gene signature" associated with IL-13-mediated dysregulation of podocyte related proteins, and subsequently to investigate the role of the differentially regulated genes in IL-13-mediated podocyte injury...
October 5, 2016: Clinical Science (1979-)
Jie Ni, Sujin Bao, Ruth I Johnson, Bingbing Zhu, Jianhua Li, Justin Vadaparampil, Christopher M Smith, Kirk N Campbell, Florian Grahammer, Tobias B Huber, John C He, Vivette D D'Agati, Andrew Chan, Lewis Kaufman
MAGI-1 is a multi-domain cytosolic scaffolding protein that in kidney is specifically located at the podocyte slit diaphragm, a specialized junction that is universally injured in proteinuric diseases. There it interacts with several essential molecules including nephrin and neph1, which are required for slit diaphragm formation and as an intracellular signaling hub. Here, we show that diminished MAGI-1 expression in cultured podocytes reduced nephrin and neph1 membrane localization and weakened tight junction integrity...
October 5, 2016: Journal of Biological Chemistry
Mengsi Hu, Minghua Fan, Junhui Zhen, Jiangong Lin, Qun Wang, Zhimei Lv, Rong Wang
Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that regulates cell adhesion, proliferation and differentiation. In the present study, a rat model of high fat diet-induced hypercholesterolaemia was established to investigate the involvement of FAK in lipid disorder-related kidney diseases. We showed focal fusion of podocyte foot process that occurred at as early as 4 weeks in rats consuming high fat diet, preceding the onset of proteinuria when aberrant phosphorylation of FAK was found...
October 5, 2016: Journal of Cellular and Molecular Medicine
Caroline Platt, Richard J Coward
Over the past two decades it has become clear that the glomerular podocyte is a key cell in preventing albuminuria, kidney failure and cardiovascular morbidity. Understanding the key pathways that protect the podocyte in times of glomerular stress, which can also be therapeutically manipulated, are highly attractive. In the following review we assess the evidence that the peroxisome proliferator activating receptor (PPAR) agonists are beneficial for podocyte and kidney function with a focus on PPAR-γ. We explain our current understanding of the mechanisms of action of these agonists and the evidence they are beneficial in diabetic and non-diabetic kidney disease...
October 3, 2016: Nephrology, Dialysis, Transplantation
Xiangling Wang, Franca Anglani, Lada Beara-Lasic, Anila J Mehta, Lisa E Vaughan, Loren Herrera Hernandez, Andrea Cogal, Steven J Scheinman, Gema Ariceta, Robert Isom, Lawrence Copelovitch, Felicity T Enders, Dorella Del Prete, Giuseppe Vezzoli, Fabio Paglialonga, Peter C Harris, John C Lieske
BACKGROUND AND OBJECTIVES: Dent disease is a rare X-linked disorder characterized by low molecular weight proteinuria and often considered a renal tubular disease. However, glomerulosclerosis was recently reported in several patients. Thus, Dent disease renal histopathologic features were characterized and assessed, and their association with kidney function was assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical renal pathology reports and slides (where available) were collected from 30 boys and men in eight countries who had undergone clinical renal biopsy between 1995 and 2014...
October 3, 2016: Clinical Journal of the American Society of Nephrology: CJASN
Natalija Filipovic, Katarina Vukojevic, Ivana Bocina, Marijan Saraga, Merica Glavina Durdov, Boris Kablar, Mirna Saraga-Babic
Differentiation of human podocytes starts with mesenchymal-to-epithelial transition (MET) of the metanephric mesenchyme into the S-shaped nephrons. During further development, differentiating podocytes regain mesenchyme-like cell characteristics by epithelial-to-mesenchymal transition (EMT), leading to formation of the terminally differentiated, non-dividing cell. Both MET and EMT processes involve changes in content and organization of cytoskeletal and actin filaments, accompanied by the increased glomerular vascularization...
October 1, 2016: Histochemistry and Cell Biology
Ellen F Carney
No abstract text is available yet for this article.
November 2016: Nature Reviews. Nephrology
K Dahan
Membranous nephropathy (MN) accounts for about 20% of cases of nephrotic syndrome in the adult. Thickening of glomerular capillary walls results from subepithelial formation of immune deposits containing IgG and the membrane attack complex of complement, which is the major mediator of proteinuria, and antigens. Idiopathic forms of MN (IMN) represent 70 to 80% of all cases. A major breakthrough was the identification of the podocyte antigen PLA2R as the target of circulating antibodies in about 70% of IMN, which confirmed that the disease was auto-immune in nature...
May 25, 2016: La Revue de Médecine Interne
Hua Tan, Hualin Yi, Weiling Zhao, Jian-Xing Ma, Yuanyuan Zhang, Xiaobo Zhou
Podocytes are mainly involved in the regulation of glomerular filtration rate (GFR) under physiological condition. Podocyte depletion is a crucial pathological alteration in diabetic nephropathy (DN) and results in a broad spectrum of clinical syndromes such as protein urine and renal insufficiency. Recent studies indicate that depleted podocytes can be regenerated via differentiation of the parietal epithelial cells (PECs), which serve as the local progenitors of podocytes. However, the podocyte regeneration process is regulated by a complicated mechanism of cell-cell interactions and cytokine stimulations, which has been studied in a piecemeal manner rather than systematically...
September 24, 2016: Oncotarget
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