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Podocyte disease

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https://www.readbyqxmd.com/read/28647853/are-podocytes-motile
#1
REVIEW
Nicole Endlich, Florian Siegerist, Karlhans Endlich
Podocytes, the postmitotic and highly branched epithelial cells of the glomerulus, play a pivotal role for the function of the glomerular filtration barrier and the development of chronic kidney disease. It has long been discussed whether podocytes in vivo are motile and can laterally migrate in a coordinated way along the capillaries until they reach the position of naked glomerular basement membrane often found in podocytopathies. Such motility would also be the prerequisite for the replacement of lost podocytes by progenitor cells...
June 24, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28646406/podocytes-and-the-quest-for-precision-medicines-for-kidney-diseases
#2
REVIEW
Peter Mundel
In this review, I describe a 30-year journey in the quest for precision medicines for patients with kidney diseases. In 1987, when I started my reseach career, most scientists studying glomerular disease biology were focused on mesangial cells. The crucial role of the podocyte in many kidney diseases characterized by proteinuria, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, had not yet been recognized. We were not aware of genetic causes or drivers of kidney diseases nor of molecular markers and cell culture systems for mechanistic studies of podocyte biology...
June 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28646076/transcriptomic-and-proteomic-profiling-provides-insight-into-mesangial-cell-function-in-iga-nephropathy
#3
Peidi Liu, Emelie Lassén, Viji Nair, Celine C Berthier, Miyuki Suguro, Carina Sihlbom, Matthias Kretzler, Christer Betsholtz, Börje Haraldsson, Wenjun Ju, Kerstin Ebefors, Jenny Nyström
IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22)...
June 23, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28645189/the-potential-role-of-retinoic-acid-receptor-%C3%AE-on-glomerulosclerosis-in-rats-and-podocytes-injury-is-associated-with-the-induction-of-mmp2-and-mmp9
#4
Xiuping Chen, Yuanhan Qin, Tianbiao Zhou, Ling Jiang, Fengying Lei, He Qin, Lei Zhang, Zhiqiang Zhou
Retinoic acid receptor α (RARα) plays a crucial role in kidney disease. However, the underlying mechanisms in glomerulosclerosis (GS) is still not clear. The roles of RARα in an adriamycin (ADR)-induced GS rat model and in ADR-induced podocyte injury in vitro were investigated. RARα was over-expressed in GS rats, and serum, urine and kidney samples were collected to detect the induction of the expression of the receptor. RARα expression was inhibited and/or over-expressed in cultured podocytes following injury, as demonstrated by morphometric assays, cell toxicity, and matrix metalloproteinase (MMP) enzymatic activity...
June 22, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28643148/mechanical-challenges-to-the-glomerulus-and-podocyte-loss-evolution-of-a-paradigm
#5
REVIEW
Kevin V Lemley
In this article, I shall outline some of the most important aspects of the evidentiary basis of the so-called Kriz model for the development of glomerular sclerosis, a model that we continue to modify to this day. In my mind, the most important findings include the fact that podocytes are generally post-mitotic cells, so that loss of a significant number for any cause leads to podocyte insufficiency. Another pivotal finding is that in many experimental models and in human disease, podocytes detach from the GBM as living cells...
June 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28640105/glomerulonephritis-and-granulomatous-vasculitis-in-kidney-as-a-complication-of-the-use-of-braf-and-mek-inhibitors-in-the-treatment-of-metastatic-melanoma-a-case-report
#6
Mehdi Maanaoui, Camille Saint-Jacques, Viviane Gnemmi, Marie Frimat, Arnaud Lionet, Marc Hazzan, Christian Noël, François Provot
RATIONALE: BRAF and MEK inhibitors have significantly improved the prognosis of metastatic melanoma, by inhibiting both the mitogen-activated protein kinase (MAP-kinase) pathway. They are associated with infrequent adverse kidney events. Most of these are related to the use of BRAF inhibitors and involve interstitial nephritis with acute tubular necrosis. PATIENT CONCERNS: We report a unique case of glomerulonephritis with renal granulomatous vasculitis in a patient diagnosed with metastatic melanoma treated with BRAF and MEK inhibitors...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639250/regulation-of-nephrin-phosphorylation-in-diabetes-and-chronic-kidney-injury
#7
Benoit Denhez, Pedro Geraldes
Diabetes is the leading cause of microalbuminuria and end-stage renal failure in industrial countries. Disruption of the filtration barrier, seen in almost all nephrotic diseases and diabetes, is the result of the loss or effacement of the podocyte foot process, notably damage of proteins within the slit diaphragm such as nephrin. For many years, nephrin has been viewed as a structural component of the slit diaphragm. It is now well recognized that nephrin contains several tyrosine residues in its cytoplasmic domain, which influences the development of glomerular injury...
June 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28636532/a-novel-pan-nox-inhibitor-apx-115-protects-kidney-injury-in-streptozotocin-induced-diabetic-mice-possible-role-of-peroxisomal-and-mitochondrial-biogenesis
#8
Guideock Kwon, Md Jamal Uddin, Gayoung Lee, Songling Jiang, Ahreum Cho, Jung Hwa Lee, Sae Rom Lee, Yun Soo Bae, Sung Hwan Moon, Soo Jin Lee, Dae Ryong Cha, Hunjoo Ha
NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are increasingly recognized as a key factor in inflammation and extracellular matrix accumulation in diabetic kidney disease. APX-115 (3-phenyl-1-(pyridin-2-yl)-4-propyl-1-5-hydroxypyrazol HCl) is a novel orally active pan-Nox inhibitor. The objective of this study was to compare the protective effect of APX-115 with a renin-angiotensin system inhibitor (losartan), the standard treatment against kidney injury in diabetic patients, on streptozotocin (STZ)-induced diabetic kidney injury...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28627612/targeted-inhibition-of-endoplasmic-reticulum-stress-new-hope-for-renal-fibrosis-review
#9
Ben Ke, Na Zhu, Fuli Luo, Yang Xu, Xiangdong Fang
Chronic kidney disease (CKD) has a very high mortality rate and remains a global health challenge. Inhibiting renal fibrosis is one of the most promising therapeutic strategies for CKD. Recent studies have indicated that endoplasmic reticulum stress (ERS) serves an active role in the development of acute and chronic kidney disease, especially with regards to renal fibrosis. In the current review, the authors summarize the latest understanding of the role of ERS during the onset of renal fibrosis. ERS promotes renal fibrosis through multiple signaling pathways, such as transforming growth factor‑β, epithelial‑mesenchymal transition and oxidative stress...
June 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626472/in-iga-nephropathy-glomerulosclerosis-is-associated-with-increased-urinary-cd80-excretion-and-urokinase-type-plasminogen-activator-receptor-positive-podocyturia
#10
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Cristian Costales-Collaguazo, Aníbal Stern, Matías Paulero, Tatiana Rengel, José Andrews, Alejandro Iotti, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Alexis Muryan, Elsa Zotta
BACKGROUND: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis...
May 2017: Nephron Extra
https://www.readbyqxmd.com/read/28625968/long-term-dose-dependent-agalsidase-effects-on-kidney-histology-in-fabry-disease
#11
Rannveig Skrunes, Camilla Tøndel, Sabine Leh, Kristin Kampevold Larsen, Gunnar Houge, Einar Skulstad Davidsen, Carla Hollak, André B P van Kuilenburg, Frédéric M Vaz, Einar Svarstad
BACKGROUND AND OBJECTIVES: Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old...
June 16, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28617070/oral-subchronic-exposure-to-silver-nanoparticles-causes-renal-damage-through-apoptotic-impairment-and-necrotic-cell-death
#12
Ratnakar Tiwari, Radha Dutt Singh, Hafizurrahman Khan, Siddhartha Gangopadhyay, Sandeep Mittal, Vikas Singh, Nidhi Arjaria, Jai Shankar, Somendu Kumar Roy, Dhirendra Singh, Vikas Srivastava
Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. Following oral exposure, AgNPs can accumulate in various organs including kidneys where they show gender specific accumulation. There is limited information on their effect on renal system following long-term animal exposure especially at the ultramicroscopic and molecular level. In this study, we have assessed the effect of 60 days oral AgNPs treatment on kidneys of female Wistar rats at doses of 50 ppm and 200 ppm that are below previously reported lowest observed adverse effect level (LOAEL)...
June 15, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28615249/reduction-in-podocyte-sirt1-accelerates-kidney-injury-in-aging-mice
#13
Peter Y Chuang, Weijing Cai, Xuezhu Li, Lu Fang, Jin Xu, Rabi Yacoub, John Cijiang He, Kyung Lee
Both the incidence and prevalence of chronic kidney disease are increasing in the elderly population. Although aging is known to induce kidney injury, the underlying molecular mechanisms remain unclear. Sirtuin 1 (Sirt1), a longevity gene, is known to protect kidney cell injury from various cellular stresses. In previous studies, we showed that the podocyte-specific loss of Sirt1 aggravates diabetic kidney injury. However, the role of Sirt1 in aging-induced podocyte injury is not known. Therefore, in this study we sought to determine the effects of podocyte-specific reduction of Sirt1 in age-induced kidney injury...
June 14, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28614117/role-of-amp-activated-protein-kinase-in-kidney-tubular-transport-metabolism-and-disease
#14
Roshan Rajani, Nuria M Pastor-Soler, Kenneth R Hallows
PURPOSE OF REVIEW: AMP-activated protein kinase (AMPK) is a metabolic sensor that regulates cellular energy balance, transport, growth, inflammation, and survival functions. This review explores recent work in defining the effects of AMPK on various renal tubular epithelial ion transport proteins as well as its role in kidney injury and repair in normal and disease states. RECENT FINDINGS: Recently, several groups have uncovered additional functions of AMPK in the regulation of kidney and transport proteins...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28611666/mineralocorticoid-receptor-signaling-as-a-therapeutic-target-for-renal-and-cardiac-fibrosis
#15
REVIEW
Greg H Tesch, Morag J Young
Activation of the mineralocorticoid receptor (MR) plays important roles in both physiological and pathological events. Blockade of MR signaling with MR antagonists (MRAs) has been used clinically to treat kidney and cardiac disease associated with hypertension and other chronic diseases, resulting in suppression of fibrosis in these organs. However, the current use of steroidal MRAs has been limited by off target effects on other hormone receptors or adverse effects on kidney tubular function. In this review, we summarize recent insights into the profibrotic roles of MR signaling in kidney and cardiovascular disease...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28611444/ep4-inhibition-attenuates-the-development-of-diabetic-and-non-diabetic-experimental-kidney-disease
#16
Karina Thieme, Syamantak Majumder, Angela S Brijmohan, Sri N Batchu, Bridgit B Bowskill, Tamadher A Alghamdi, Suzanne L Advani, M Golam Kabir, Youan Liu, Andrew Advani
The therapeutic targeting of prostanoid subtype receptors may slow the development of chronic kidney disease (CKD) through mechanisms that are distinct from those of upstream COX inhibition. Here, employing multiple experimental models of CKD, we studied the effects of inhibition of the EP4 receptor, one of four receptor subtypes for the prostanoid prostaglandin E2. In streptozotocin-diabetic endothelial nitric oxide synthase knockout mice, EP4 inhibition attenuated the development of albuminuria, whereas the COX inhibitor indomethacin did not...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606850/the-impact-of-%C3%AE-lipoic-acid-on-cell-viability-and-expression-of-nephrin-and-znf580-in-normal-human-podocytes
#17
Ulrike Leppert, Allan Gillespie, Miriam Orphal, Karen Böhme, Claudia Plum, Kaj Nagorsen, Janine Berkholz, Reinhold Kreutz, Andreas Eisenreich
Human podocytes (hPC) are essential for maintaining normal kidney function and dysfunction or loss of hPC play a pivotal role in the manifestation and progression of chronic kidney diseases including diabetic nephropathy. Previously, α-Lipoic acid (α-LA), a licensed drug for treatment of diabetic neuropathy, was shown to exhibit protective effects on diabetic nephropathy in vivo. However, the effect of α-LA on hPC under non-diabetic conditions is unknown. Therefore, we analyzed the impact of α-LA on cell viability and expression of nephrin and zinc finger protein 580 (ZNF580) in normal hPC in vitro...
June 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28606243/-research-advances-in-the-protective-effect-of-all-trans-retinoic-acid-against-podocyte-injury
#18
Xiu-Ping Chen, Yuan-Han Qin
All-trans retinoic acid (ATRA) is a vitamin A derivative and plays an important role in the regulation of cell aggregation, differentiation, apoptosis, proliferation, and inflammatory response. In recent years, some progress has been made in the role of ATRA in renal diseases, especially its protective effect on podocytes. This article reviews the research advances in podocyte injury, characteristics of ATRA, podocyte differentiation and regeneration induced by ATRA, and the protective effect of ATRA against proliferation, deposition of fibers, and apoptosis...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28597189/a-podocyte-view-of-membranous-nephropathy-from-heymann-nephritis-to-the-childhood-human-disease
#19
REVIEW
Pierre Ronco, Hanna Debiec
Membranous nephropathy (MN) is characterized by an accumulation of immune deposits on the subepithelial side of the glomerular basement membrane, which results in complement activation and proteinuria. Since 2002, several major antigens of the podocyte have been identified in human MN, the first one being neutral endopeptidase (NEP), the alloantigen involved in neonatal cases of MN that occur in newborns from NEP-deficient mothers. This discovery opened the field to the major advances that have occurred since then in the pathophysiology and treatment of MN...
June 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28596971/soluble-urokinase-receptor-and-the-kidney-response-in-diabetes-mellitus
#20
REVIEW
Ranadheer R Dande, Vasil Peev, Mehmet M Altintas, Jochen Reiser
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. DN typically manifests by glomerular hyperfiltration and microalbuminuria; then, the disease progresses to impaired glomerular filtration rate, which leads to ESRD. Treatment options for DN include the strict control of blood glucose levels and pressure (e.g., intraglomerular hypertension). However, the search for novel therapeutic strategies is ongoing. These include seeking specific molecules that contribute to the development and progression of DN to potentially interfere with these "molecular targets" as well as with the cellular targets within the kidney such as podocytes, which play a major role in the pathogenesis of DN...
2017: Journal of Diabetes Research
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