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Yukio Ozaki, Shogo Tamura, Katsue Suzuki-Inoue
Platelets play a key role in the pathophysiological processes of hemostasis and thrombus formation. However, platelet functions beyond thrombosis and hemostasis have been increasingly identified in recent years. A large body of evidence now exists which suggests that platelets also play a key role in inflammation, immunity, malignancy, and furthermore in organ development and regeneration, such as the liver. We have recently identified CLEC-2 on the platelet membrane, which induces intracellular activation signals upon interaction of a snake venom, rhodocytin...
2016: Thrombosis Journal
Leandro Z Crivellenti, Gyl E B Silva, Sofia Borin-Crivellenti, Rachel Cianciolo, Christopher A Adin, Márcio Dantas, Denner S Dos Anjos, Mirela Tinucci-Costa, Aureo E Santana
The incidence and prevalence of paraneoplastic glomerulopathy, especially associated with carcinoma, are a matter of debate and the causal link between cancer and glomerular diseases remains unclear. The aim of this study was to evaluate renal biopsies of selected bitches with spontaneous mammary gland carcinoma. We hypothesized that dogs with mammary carcinomas would show histologic evidence of glomerular pathology. A prospective study was performed in dogs with naturally occurring mammary carcinoma that were undergoing tumor resection and ovariohysterectomy...
2016: PloS One
Shigeru Shibata, Kenichi Ishizawa, Shunya Uchida
The kidney has a central role in long-term control of blood pressure, and decreased kidney function is a common but difficult-to-treat cause of hypertension. Conversely, elevated blood pressure contributes to the progression of chronic kidney disease. Steroid hormone aldosterone and its receptor mineralocorticoid receptor (MR) contribute to hypertension by increasing renal salt reabsorption and promote kidney dysfunction through direct effects on renal parenchymal cells. Accumulating data indicate that various mechanisms affect aldosterone-MR signaling...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Eugen Widmeier, Weizhen Tan, Merlin Airik, Friedhelm Hildebrandt
INTRODUCTION: Steroid-resistant nephrotic syndrome (SRNS) inevitably progresses to end-stage kidney disease, requiring dialysis or transplantation for survival. However, treatment modalities and drug discovery remain limited. Mutations in over 30 genes have been discovered as monogenic causes of SRNS. Most of these genes are predominantly expressed in the glomerular epithelial cell, the podocyte, placing it at the center of the pathogenesis of SRNS. Podocyte migration rate (PMR) represents a relevant intermediate phenotype of disease in monogenic causes of SRNS...
October 19, 2016: American Journal of Physiology. Renal Physiology
Jianyin Long, Shawn S Badal, Zengchun Ye, Yin Wang, Bernard A Ayanga, Daniel L Galvan, Nathanael H Green, Benny H Chang, Paul A Overbeek, Farhad R Danesh
The regulatory roles of long noncoding RNAs (lncRNAs) in transcriptional coactivators are still largely unknown. Here, we have shown that the peroxisome proliferator-activated receptor γ (PPARγ) coactivator α (PGC-1α, encoded by Ppargc1a) is functionally regulated by the lncRNA taurine-upregulated gene 1 (Tug1). Further, we have described a role for Tug1 in the regulation of mitochondrial function in podocytes. Using a murine model of diabetic nephropathy (DN), we performed an unbiased RNA-sequencing (RNA-seq) analysis of kidney glomeruli and identified Tug1 as a differentially expressed lncRNA in the diabetic milieu...
October 17, 2016: Journal of Clinical Investigation
Szu Yuan Li, Katalin Susztak
An increasing amount of evidence suggests that metabolic alterations play a key role in chronic kidney disease (CKD) pathogenesis. In this issue of the JCI, Long et al. report that the long noncoding RNA (lncRNA) taurine-upregulated 1 (Tug1) contributes to CKD development. The authors show that Tug1 regulates mitochondrial function in podocytes by epigenetic targeting of expression of the transcription factor PPARγ coactivator 1α (PGC-1α, encoded by Ppargc1a). Transgenic overexpression of Tug1 specifically in podocytes ameliorated diabetes-induced CKD in mice...
October 17, 2016: Journal of Clinical Investigation
Sybille Koehler, Sebastian Brähler, Alexander Kuczkowski, Julia Binz, Matthias J Hackl, Henning Hagmann, Martin Höhne, Merly C Vogt, Claudia M Wunderlich, F Thomas Wunderlich, Frank Schweda, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by a Designer Drug) knock-in mouse line to manipulate intracellular Ca(2+) levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca(2+) peaks on podocyte biology in living animals...
October 19, 2016: Scientific Reports
Cristina Zennaro, Maria Pia Rastaldi, Gerald James Bakeine, Riccarda Delfino, Federica Tonon, Rossella Farra, Gabriele Grassi, Mary Artero, Massimo Tormen, Michele Carraro
Although it is well recognized that cell-matrix interactions are based on both molecular and geometrical characteristics, the relationship between specific cell types and the three-dimensional morphology of the surface to which they are attached is poorly understood. This is particularly true for glomerular podocytes - the gatekeepers of glomerular filtration - which completely enwrap the glomerular basement membrane with their primary and secondary ramifications. Nanotechnologies produce biocompatible materials which offer the possibility to build substrates which differ only by topology in order to mimic the spatial organization of diverse basement membranes...
2016: International Journal of Nanomedicine
Yu Guan, Daisuke Nakano, Zhang Yifan, Akira Nishiyama
OBJECTIVE: Previous studies have indicated the beneficial effects of N-type calcium channel blocker, cilnidipine, on protecting renal podocyte injury in metabolic syndrome model rats. In the present study, we examined the effects of cilnidipine (L/N-type calcium channel blocker) and nifedipine (L-type calcium channel blocker) on the glomerular filtration barrier damage in the doxorubicin-induced nephropathy mice model. DESIGN AND METHOD: Balb/c mice (male, 5 week-old) were treated with vehicle (n = 5), doxorubicin (20 mg/kg, i...
September 2016: Journal of Hypertension
Yoshitsugu Iwakura, Ryo Morimoto, Kumi Kikuchi, Yoshikiyo Ono, Yuta Tezuka, Yasuko Tsukada, Masahiro Nezu, Yasuhiro Igarashi, Masataka Kudo, Akira Nishiyama, Sadayoshi Ito, Fumitoshi Satoh
OBJECTIVE: High prevalence of renal damage has been demonstrated in patients with primary aldosteronism (PA). However, the original mechanism and onset still be elucidated. The purpose of this study is to investigate the possible original mechanisms of renal damages in PA. DESIGN AND METHOD: Consecutive 72 patients with aldosterone producing adenoma (APA) and 70 patients with essential hypertension (EH) participated. No patients had renal damages defined as eGFR (based on Cystatin C) < 60 ml/min/1...
September 2016: Journal of Hypertension
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
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