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https://www.readbyqxmd.com/read/28719912/crocin-protects-podocytes-against-oxidative-stress-and-inflammation-induced-by-high-glucose-through-inhibition-of-nf-%C3%AE%C2%BAb
#1
Sutong Li, Xiaoxia Liu, Jie Lei, Junle Yang, Puxun Tian, Yi Gao
BACKGROUND/AIMS: Diabetic nephropathy (DN) is a microangiopathic disease characterized by excessive urinary albumin excretion, which occurs in 30% of patients with diabetes mellitus. It is the second leading cause of end-stage renal diseases in China. Nuclear factor-kappa B (NF-κB) is reported to be closely correlated with the inflammation underlying diabetes-associated renal damage. Crocin, a plant-derived compound, has antioxidant properties that may inhibit NF-κB. METHODS: In the present study, we used a conditionally immortalized mouse podocyte cell line to explore whether crocin could effectively block albuminuria...
July 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28719898/role-of-mir-155-signal-pathway-in-regulating-podocyte-injury-induced-by-tgf-%C3%AE-1
#2
Xu Lin, Xintng Zhen, Haiting Huang, Haohao Wu, Yanwu You, Pengwei Guo, Xiangjun Gu, Fafen Yang
BACKGROUND/AIMS: Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of miR-155 on podocyte injury induced by TGF-β1 and to determine further molecular mediators involved in the effects of miR-155. METHODS: Conditionally immortalized podocytes were cultured in vitro and they were divided into four groups: control; TGF-β1 treatment; TGF-β1 with miR-155 knockdown [using antisense oligonucleotides against miR-155 (ASO-miR-155)] and TGF-β1 with negative control antisense oligonucleotides (ASO-NC)...
July 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28717874/distinct-functions-of-crumbs-regulating-slit-diaphragms-and-endocytosis-in-drosophila-nephrocytes
#3
Florian Hochapfel, Lucia Denk, Gudrun Mendl, Ulf Schulze, Christine Maaßen, Yulia Zaytseva, Hermann Pavenstädt, Thomas Weide, Reinhard Rachel, Ralph Witzgall, Michael P Krahn
Mammalian podocytes, the key determinants of the kidney's filtration barrier, differentiate from columnar epithelial cells and several key determinants of apical-basal polarity in the conventional epithelia have been shown to regulate podocyte morphogenesis and function. However, little is known about the role of Crumbs, a conserved polarity regulator in many epithelia, for slit-diaphragm formation and podocyte function. In this study, we used Drosophila nephrocytes as model system for mammalian podocytes and identified a conserved function of Crumbs proteins for cellular morphogenesis, nephrocyte diaphragm assembly/maintenance, and endocytosis...
July 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28716959/podocyte-growing-pains-in-adaptive-fsgs
#4
EDITORIAL
Vivette D D'Agati
No abstract text is available yet for this article.
July 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28709640/genome-wide-identification-of-genes-essential-for-podocyte-cytoskeletons-based-on-single-cell-rna%C3%A2-sequencing
#5
Yuqiu Lu, Yuting Ye, Wenduona Bao, Qianqian Yang, Jinquan Wang, Zhihong Liu, Shaolin Shi
Gene expression differs substantially among individual cells of the same type. We speculate that genes that are expressed in all but a portion of cells of a given cell type would be likely essential and required for either the cell survival (housekeeping) or for the cell type's unique structure and function, enabling the organism to survive. Here, we performed RNA-seq of 20 mouse podocytes using the Fluidigm C1 system and identified 335 genes that were expressed in all of them. Among them, 239 genes were also expressed in mesangial and endothelial cells and were involved in energy metabolism, protein synthesis, etc...
July 11, 2017: Kidney International
https://www.readbyqxmd.com/read/28709637/tubulointerstitial-fibrosis-can-sensitize-the-kidney-to-subsequent-glomerular-injury
#6
Beom Jin Lim, Jae Won Yang, Jun Zou, Jianyong Zhong, Taiji Matsusaka, Ira Pastan, Ming-Zhi Zhang, Raymond C Harris, Hai-Chun Yang, Agnes B Fogo
Chronic glomerular injury is associated with eventual development of tubulointerstitial fibrosis. Here we aimed to assess whether, and how, mild chronic tubulointerstitial injury affects glomeruli. For this, we generated mice expressing different toxin receptors, one on their proximal tubular epithelial cells (diphtheria toxin receptor [DTR]) and the other only on podocytes (human CD25 [IL-2R] driven by the nephrin promoter [Nep25]), allowing serial induction of tubule-specific and glomerular (podocyte)-specific injury, respectively...
July 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28709595/losing-their-footing-rac1-signaling-causes-podocyte-detachment-and-fsgs
#7
Gentzon Hall, Robert F Spurney
Selective modulation of Rho GTPase activity in podocytes recapitulates characteristic features of human nephrosis. Using a mouse model, Robins et al. found that high levels of Rac1 activation in podocytes caused podocyte detachment and glomerulosclerosis. Podocyte Rac1 activity was enhanced in biopsy specimens from patients with nephrosis, and serum from this patient population activated Rac1 in cultured podocytes. These data provide a causal link between podocyte Rac1 activation and human nephrotic diseases...
August 2017: Kidney International
https://www.readbyqxmd.com/read/28707483/investigational-drugs-in-development-for-focal-segmental-glomerulosclerosis
#8
Howard Trachtman
Focal segmental glomerulosclerosis is an important cause of end stage kidney disease and is a paradigm for the study of glomerular scarring. There are no FDA approved treatments for this condition. Current therapies, assessed based on reduction in proteinuria, are generally effective in a subset of patients which suggests that FSGS is a heterogeneous group of glomerular disorders or podocytopathies that converge on a common histopathological phenotype. Areas covered: We searched for investigational drugs agents that target different pathophysiological pathways using the key words 'FSGS' and 'podocyte' in American and European clinical trial registers (clinicaltrials...
July 14, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28696248/intracellular-apol1-risk-variants-cause-cytotoxicity-accompanied-by-energy-depletion
#9
Daniel Granado, Daria Müller, Vanessa Krausel, Etty Kruzel-Davila, Christian Schuberth, Melanie Eschborn, Roland Wedlich-Söldner, Karl Skorecki, Hermann Pavenstädt, Ulf Michgehl, Thomas Weide
Population genetic approaches have uncovered a strong association between kidney diseases and two sequence variants of the APOL1 gene, called APOL1 risk variant G1 and variant G2, compared with the nonrisk G0 allele. However, the mechanism whereby these variants lead to disease manifestation and, in particular, whether this involves an intracellular or extracellular pool of APOL1 remains unclear. Herein, we show a predominantly intracellular localization of APOL1 G0 and the renal risk variants, which localized to membranes of the endoplasmic reticulum in podocyte cell lines...
July 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28689240/supar-and-chronic-kidney-disease-a-podocyte-story
#10
REVIEW
Martin Zeier, Jochen Reiser
The soluble urokinase-type plasminogen activator receptor (suPAR) is a circulating signaling molecule derived from immature myeloid cells. Elevated levels of suPAR have been linked to the pathogenesis of the kidney disease focal and segmental glomerulosclerosis. Here, suPAR acts on podocytes by activating αvβ3 integrins. Large observational studies showed that suPAR also predicts chronic kidney disease incidence and progression by predating the disease by several years prior to any other known marker of renal dysfunction...
July 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28687864/stressed-podocytes-mechanical-forces-sensors-signaling-and-response
#11
REVIEW
Karlhans Endlich, Felix Kliewe, Nicole Endlich
Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress...
July 7, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28687614/signal-integration-at-the-pi3k-p85-xbp1-hub-endows-coagulation-protease-activated-protein-c-with-insulin-like-function
#12
Thati Madhusudhan, Hongjie Wang, Sanchita Ghosh, Wei Dong, Varun Kumar, Moh'd Mohanad Al-Dabet, Jayakumar Manoharan, Sumra Nazir, Ahmed Elwakiel, Fabian Bock, Shrey Kohli, Andi Marquardt, Ibrahim Sögüt, Khurrum Shahzad, Andreas J Müller, Charles T Esmon, Peter P Nawroth, Jochen Reiser, Triantafyllos Chavakis, Wolfram Ruf, Berend Isermann
Coagulation proteases have increasingly recognized functions beyond hemostasis and thrombosis. Disruption of activated protein C (aPC) or insulin signaling both impair function of podocytes and ultimately cause dysfunction of the glomerular filtration barrier and diabetic kidney disease (DKD). We here show that insulin and aPC converge on a common spliced-X-box binding protein-1 (sXBP1) signaling pathway to maintain endoplasmic reticulum (ER)-homeostasis. Analogous to insulin, physiological levels of aPC maintain endoplasmic reticulum (ER) proteostasis in DKD...
July 7, 2017: Blood
https://www.readbyqxmd.com/read/28686869/modeling-the-glomerular-filtration-barrier-are-you-kidney-ing-me
#13
Paola Romagnani, Laura Lasagni
Podocyte depletion drives kidney disease and kidney failure progression, but podocyte complexity at the glomerular filtration barrier is difficult to model in vitro. In Nature Biomedical Engineering, Musah et al. (2017) developed a multifluidic device with iPS-derived podocytes mimicking a functional glomerular filtration barrier that elevates standards for modeling glomerular diseases.
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28685678/glomerular-endothelium-and-its-impact-on-glomerular-filtration-barrier-in-diabetes-are-the-gaps-still-illusive
#14
Joseph Fomusi Ndisang
BACKGROUND: Glomerular capillaries are lined with highly specialized fenestrated endothelium which are primarily responsible to regulate high flux filtration of fluid and small solutes. During filtration, plasma passes through the fenestrated endothelium and basement membrane before it reaches the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocytes. METHODS: A PubMed search was done for recent articles on components of the glomerular filtration barrier such as glomerular endothelial cells, podocytes and glomerular basement membrane, and the effect of diabetes on these structures...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28682562/-renal-diseases-related-to-myh9-disorders
#15
Dario Galeano, Luca Zanoli, Vincenzo L'Imperio, Pasquale Fatuzzo, Antonio Granata
Mutations in MYH9 gene encoding the nonmuscle myosin heavy chain IIA (NMMHC-IIA) are related to a number of rare autosomal-dominant disorders which has been known as May-Hegglin disease, Sebastian syndrome, Fechtner syndrome and Epstein syndrome. Their common clinical features are congenital macrothrombocytopaenia and polymorphonuclear inclusion bodies, in addition to a variable risk of developing proteinuria, chronic kidney disease progressing toward end stage, sensorineural deafness and presenile cataracts...
April 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28682034/-fabry-s-disease-an-example-of-cardiorenal-syndrome-type-5
#16
Gianluca Villa, Stefano Romagnoli, Aashish Sharma, Claudio Ronco
Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28681095/nail-patella-syndrome
#17
REVIEW
Ralph Witzgall
The pathognomonic symptoms of patients with nail-patella syndrome are their small or absent patellae and dysplastic or absent finger- and toenails. Many of the patients suffer from renal symptoms which also affect their prognosis. In 1998, mutations in the gene encoding the transcription factor LMX1B were identified as underlying this autosomal-dominant disease. The LMX1B gene is expressed in a variety of tissues, and the symptoms are reflected nicely by its expression pattern. LMX1B is essential for dorso-ventral pattern formation in the limbs, for differentiation of the anterior portions of the eyes, for development of certain neuron populations in the central nervous system, and for the differentiation and maintenance of podocytes...
July 5, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28680430/human-alpha-galactosidases-transiently-produced-in-nicotiana-benthamiana-leaves-new-insights-in-substrate-specificities-with-relevance-for-fabry-disease
#18
Kassiani Kytidou, Thomas J M Beenakker, Lotte B Westerhof, Cornelis H Hokke, Geri F Moolenaar, Nora Goosen, Mina Mirzaian, Maria J Ferraz, Mark de Geus, Wouter W Kallemeijn, Herman S Overkleeft, Rolf G Boot, Arjen Schots, Dirk Bosch, Johannes M F G Aerts
Deficiency of α-galactosidase A (α-GAL) causes Fabry disease (FD), an X-linked storage disease of the glycosphingolipid globtriaosylcerammide (Gb3) in lysosomes of various cells and elevated plasma globotriaosylsphingosine (Lyso-Gb3) toxic for podocytes and nociceptive neurons. Enzyme replacement therapy is used to treat the disease, but clinical efficacy is limited in many male FD patients due to development of neutralizing antibodies (Ab). Therapeutic use of modified lysosomal α-N-acetyl-galactosaminidase (α-NAGAL) with increased α-galactosidase activity (α-NAGAL(EL)) has therefore been suggested...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28677767/lysyl-oxidase%C3%A2-like-2-is-expressed-in-kidney-tissue-and-is-associated-with-the-progression-of-tubulointerstitial-fibrosis
#19
Sung-Eun Choi, Nara Jeon, Hoon Young Choi, Jae Il Shin, Hyeon Joo Jeong, Beom Jin Lim
Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis...
July 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28676854/dab1-contributes-to-angiotensin-ii-induced-apoptosis-via-p38-signaling-pathway-in-podocytes
#20
Zhao Gao, Xinghua Chen, Kai Zhu, Ping Zeng, Guohua Ding
Numerous studies have found that angiotensin II (Ang II) participates in podocyte apoptosis and exacerbates progression of end-stage kidney disease (ESKD). However, its underlying mechanism remains largely unexplored. As a homolog of Drosophila disabled (Dab) protein, Dab1 plays a vital role in cytoskeleton, neuronal migration, and proliferation. In the present study, our data revealed that Ang II-infused rats developed hypertension, proteinuria, and podocyte injury accompanied by Dab1 phosphorylation and increased reelin expression in kidney...
2017: BioMed Research International
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