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https://www.readbyqxmd.com/read/28550082/primary-membranous-nephropathy
#1
William G Couser
Membranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%-5%)...
May 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28550045/pacsin2-accelerates-nephrin-trafficking-and-is-up-regulated-in-diabetic-kidney-disease
#2
Vincent Dumont, Tuomas A Tolvanen, Sara Kuusela, Hong Wang, Tuula A Nyman, Sonja Lindfors, Jukka Tienari, Harry Nisen, Shiro Suetsugu, Markus Plomann, Hiroshi Kawachi, Sanna Lehtonen
Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker Diabetic Fatty (ZDF) rats that have altered renal function...
May 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28546764/optimal-management-of-primary-focal-segmental-glomerulosclerosis-in-adults
#3
REVIEW
Séverine Beaudreuil, Hans Kristian Lorenzo, Michele Elias, Erika Nnang Obada, Bernard Charpentier, Antoine Durrbach
Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular kidney disease that is revealed by proteinuria or even nephrotic syndrome. A diagnosis can be established from a kidney biopsy that shows focal and segmental glomerulosclerosis. This histopathological lesion may be caused by a primary podocyte injury (idiopathic FSGS) but is also associated with other pathologies (secondary FSGS). The first-line treatment for idiopathic FSGS with nephrotic syndrome is a prolonged course of corticosteroids. However, steroid resistance or steroid dependence is frequent, and despite intensified immunosuppressive treatment, FSGS can lead to end-stage renal failure...
2017: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/28544564/podocyte-activation-of-nlrp3-inflammasomes-contributes-to-the-development-of-proteinuria-in-lupus-nephritis
#4
Rong Fu, Chaohuan Guo, Shuang Wang, Yuefang Huang, Ou Jin, Haoqiang Hu, Jingxian Chen, Bihua Xu, Mianjing Zhou, Jijun Zhao, Sun-Sang J Sung, Hongyang Wang, Felicia Gaskin, Niansheng Yang, Shu-Man Fu
Objective Development of proteinuria in lupus nephritis (LN) is associated with podocyte dysfunction. The NLRP3 inflammasome has been implicated in the pathogenesis of LN. This study investigates whether NLRP3 inflammasome activation is involved in the development of podocyte injury in LN. Methods A fluorescence-labeled caspase-1 inhibitor probe was used to detect the activation of NLRP3 inflammasomes in podocytes in lupus-prone NZM2328 mice and in renal biopsies from LN patients. MCC950, a selective inhibitor of NLRP3, was used to treat NZM2328 mice...
May 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28539358/protein-kinase-c-%C3%AE%C2%B5-stabilizes-%C3%AE-catenin-and-regulates-its-subcellular-localization-in-podocytes
#5
Michelle Duong, Xuejiao Yu, Beina Teng, Patricia Schroder, Hermann Haller, Susanne Eschenburg, Mario Schiffer
Kidney disease has been linked to dysregulated signaling via protein kinase C (PKC) in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of β-catenin, which promotes its degradation. β-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. However, whether other PKC isoforms interact with β-catenin has not been studied systematically. Here we demonstrate that PKCε-deficient mice, which develop proteinuria and glomerulosclerosis, display a lower β-catenin expression compared to PKC wildtype mice, consistent with an altered phenotype of podocytes in culture...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28536464/the-protective-effect-of-human-renal-sinus-fat-on-glomerular-cells-is-reversed-by-the-hepatokine-fetuin-a
#6
R Wagner, J Machann, M Guthoff, P P Nawroth, S Nadalin, M A Saleem, N Heyne, A Königsrainer, F Fend, F Schick, A Fritsche, N Stefan, H-U Häring, E Schleicher, D I Siegel-Axel
Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536193/the-ferm-protein-epb41l5-regulates-actomyosin-contractility-and-focal-adhesion-formation-to-maintain-the-kidney-filtration-barrier
#7
Christoph Schell, Manuel Rogg, Martina Suhm, Martin Helmstädter, Dominik Sellung, Mako Yasuda-Yamahara, Oliver Kretz, Victoria Küttner, Hani Suleiman, Laxmikanth Kollipara, René P Zahedi, Albert Sickmann, Stefan Eimer, Andrey S Shaw, Albrecht Kramer-Zucker, Mariko Hirano-Kobayashi, Takaya Abe, Shinichi Aizawa, Florian Grahammer, Björn Hartleben, Jörn Dengjel, Tobias B Huber
Podocytes form the outer part of the glomerular filter, where they have to withstand enormous transcapillary filtration forces driving glomerular filtration. Detachment of podocytes from the glomerular basement membrane precedes most glomerular diseases. However, little is known about the regulation of podocyte adhesion in vivo. Thus, we systematically screened for podocyte-specific focal adhesome (FA) components, using genetic reporter models in combination with iTRAQ-based mass spectrometry. This approach led to the identification of FERM domain protein EPB41L5 as a highly enriched podocyte-specific FA component in vivo...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28535513/pkc-%C3%AE-triggers-egfr-ubiquitination-endocytosis-and-erk-activation-in-podocytes-stimulated-with-high-glucose
#8
Chun-Tao Lei, Yan-Hong Wei, Hui Tang, Qian Wen, Chen Ye, Chun Zhang, Hua Su
BACKGROUND: Protein Kinase C-α (PKC-α) and epidermal growth factor receptor (EGFR) are both involved in diabetic kidney disease; however, the connection between these two proteins during high glucose-induced podocyte injury remains uncertain. METHODS: Diabetes was induced in SD rats by streptozotocin (STZ). Fourteen days later, the kidney cortex was removed and subjected to plasma membrane isolation and lipid raft fractionation. In vitro study human podocyte cell line was differentiated and subjected to various treatments...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534128/cathepsin-l-activity-correlates-with-proteinuria-in-chronic-kidney-disease-in-humans
#9
Yu Cao, Xing Liu, Ying Li, Yao Lu, Hua Zhong, Weihong Jiang, Alex F Chen, Timothy R Billiar, Hong Yuan, Jingjing Cai
BACKGROUND: The presence and severity of proteinuria is considered an important prognostic marker in patients with chronic kidney disease (CKD) and is associated with mortality and morbidity. Cathepsin L is highly expressed in the foot processes of podocytes in the kidney, which serves as an ultrafiltration barrier. Cathepsin L is also up-regulated in the setting of inflammation as a feature of CKD. Therefore, we postulated that proteinuria severity in CKD patients might correlate with increased serum levels of cathepsin L...
May 22, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#10
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28528353/adrenomedullin-ameliorates-podocyte-injury-induced-by-puromycin-aminonucleoside-in-vitro-and-in-vivo-through-modulation-of-rho-gtpases
#11
Nan Dong, Lixia Meng, Ruqun Xue, Meng Yu, Zhonghua Zhao, Xueguang Liu
PURPOSE: Podocyte injury is a key event in proteinuric kidney disease and eventually glomerular scarring. While adrenomedullin (AM), a potent vasodilatory peptide, has been reported to confer renoprotection in several experimental models of kidney diseases, its effect on injured podocytes and the related mechanism is still largely unknown. METHODS: Employing Western blotting analysis, immunoprecipitation and immunofluorescence, we investigated the effects of AM on the expressions of podocyte cytoskeletal proteins and Rho-family small GTPases (Rho GTPases) in puromycin aminonucleoside (PAN)-induced podocyte injury, both in cultured podocytes and in PAN nephrosis rats...
May 20, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28523190/expression-of-upar-in-urinary-podocytes-of-patients-with-fabry-disease
#12
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Juan Politei, Cristian Costales-Collaguazo, Aníbal Stern, Matías Paulero, Tatiana Rengel, Lara Valiño-Rivas, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Alexis Muryan, Alberto Ortiz, María Dolores Sanchez-Niño, Elsa Zotta
Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-β (n = 21)...
2017: International Journal of Nephrology
https://www.readbyqxmd.com/read/28516997/peptide-and-antibody-ligands-for-renal-targeting-nanomedicine-strategies-for-kidney-disease
#13
Jonathan Wang, Jacqueline J Masehi-Lano, Eun Ji Chung
The kidney is one of the body's main filtration organs, and hence, opportunity exists for designing nanomedicine that can naturally accumulate in the kidneys for renal diseases. In addition to traditional physiochemical properties for kidney accumulation, such as size and charge, synthesized nanoparticles can be conjugated with targeting ligands which further home the nanocarriers to cell types of interest. In this review, we highlight key studies that have shown success in utilizing peptide- or antibody-based ligands in nanoparticles to target the glomerulus, podocytes, or renal tubule cells in the kidney...
May 18, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28512641/podocyte-autophagy-a-potential-therapeutic-target-to-prevent-the-progression-of-diabetic-nephropathy
#14
REVIEW
Na Liu, Liuqing Xu, Yingfeng Shi, Shougang Zhuang
Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD), becomes a worldwide problem. Ultrastructural changes of the glomerular filtration barrier, especially the pathological changes of podocytes, lead to proteinuria in patients with diabetes. Podocytes are major components of glomerular filtration barrier, lining outside of the glomerular basement membrane (GBM) to maintain the permeability of the GBM. Autophagy is a high conserved cellular process in lysosomes including impaired protein, cell organelles, and other contents in the cytoplasm...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28508947/podocytes-from-the-diagnostic-and-therapeutic-point-of-view
#15
REVIEW
Janina Müller-Deile, Mario Schiffer
The central role of podocytes in glomerular diseases makes this cell type an interesting diagnostic tool as well as a therapeutic target. In this review, we discuss the current literature on the use of podocytes and podocyte-specific markers as non-invasive diagnostic tools in different glomerulopathies. Furthermore, we highlight the direct effects of drugs currently used to treat primary glomerular diseases and describe their direct cellular effects on podocytes. A new therapeutic potential is seen in drugs targeting the podocytic actin cytoskeleton which is essential for podocyte foot process structure and function...
May 16, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28501082/a-high-content-screening-technology-for-quantitatively-studying-podocyte-dynamics
#16
REVIEW
Jochen Reiser, Ha Won Lee, Vineet Gupta, Mehmet M Altintas
Podocytes form the visceral layer of a kidney glomerulus and express a characteristic octopus-like cellular architecture specialized for the ultrafiltration of blood. The cytoskeletal dynamics and structural elasticity of podocytes rely on the self-organization of highly interconnected actin bundles, and the maintenance of these features is important for the intact glomerular filtration. Development of more differentiated podocytes in culture has dramatically increased our understanding of the molecular mechanisms regulating podocyte actin dynamics...
May 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28491286/unwinding-focal-segmental-glomerulosclerosis
#17
REVIEW
Vasil Peev, Eunsil Hahm, Jochen Reiser
Focal segmental glomerulosclerosis (FSGS) represents the most common primary glomerular disease responsible for the development of end-stage renal disease (ESRD) in the United States (US). The disease progresses from podocyte injury to chronic kidney disease (CKD), ultimately leading to total nephron degeneration. Extensive basic science research has been conducted to unwind the mechanisms of FSGS and, with those insights, understand major contributors of CKD in general. As a result, several putative molecules and pathways have been studied, all implicated in the disease; some serve, in addition, as early biomarkers...
2017: F1000Research
https://www.readbyqxmd.com/read/28490532/podocyte-specific-knockout-ko-of-cyclooxygenase-2-cox2-exacerbates-diabetic-kidney-disease
#18
Limng Wang, Yonggang Sha, Jingyi Bai, William Eisner, Mathew A Sparks, Anne F Buckley, Robert F Spurney
Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to glomerular injury in diabetic kidney disease, but some basal level of podocyte COX2 expression might be required to promote podocyte attachment and/or survival. To investigate the role of podocyte COX2 expression in diabetic kidney disease, we deleted COX2 specifically in podocytes in a mouse model of type 1 diabetes mellitus (Akita mice). Podocyte specific knockout (KO) of COX2 did not affect renal morphology or albuminuria in non-diabetic mice...
May 10, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28488220/pla2r-positive-primary-membranous-nephropathy-in-a-child-with-ipex-syndrome
#19
Teresa Chuva, Frederick Pfister, Ortraud Beringer, Kerstin Felgentreff, Maike Büttner-Herold, Kerstin Amann
BACKGROUND: Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare primary immunodeficiency syndrome characterized by the development of multiple autoimmune disorders in affected individuals. Different forms of renal injury have been reported in IPEX syndrome, and membranous nephropathy (MN) is among the most common glomerulopathies found. However, the exact pathogenesis of MN in this setting has not been elucidated, and it is not clear whether it is part of the clinical spectrum of the disease or secondary to medications, infections or other concomitant insults...
May 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28484847/genetic-kidney-diseases-caenorhabditis-elegans-as-model-system
#20
REVIEW
Athina Ganner, Elke Neumann-Haefelin
Despite its apparent simplicity, the nematode Caenorhabditis elegans has a high rating as a model in molecular and developmental biology and biomedical research. C. elegans has no excretory system comparable with the mammalian kidney but many of the genes and molecular pathways involved in human kidney diseases are conserved in C. elegans. The plethora of genetic, molecular and imaging tools available in C. elegans has enabled major discoveries in renal research and advanced our understanding of the pathogenesis of genetic kidney diseases...
May 8, 2017: Cell and Tissue Research
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