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Podocyte disease

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https://www.readbyqxmd.com/read/29452609/screening-drugs-for-kidney-disease-targeting-the-podocyte
#1
Joshua S Bryer, Katalin Susztak
Podocytes cover the kidney glomerular basement membrane and present the final barrier in the renal filtration system. Podocyte loss, observed in most kidney diseases, correlates with kidney function decline. In this issue of Cell Chemical Biology, Seiber et al. (2018), using a high-throughput chemical screen, identified the compound CDG-0876, which improved podocyte survival.
February 15, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29449955/prospects-for-precision-medicine-in-glomerulonephritis-treatment
#2
REVIEW
Yulu Cherry Liu, Justin Chun
Background: Glomerulonephritis (GN) consists of a group of kidney diseases that are categorized based on shared histopathological features. The current classifications for GN make it difficult to distinguish the individual variability in presentation, disease progression, and response to treatment. GN is a significant cause of end-stage renal disease (ESRD), and improved therapies are desperately needed because current immunosuppressive therapies sometimes lack efficacy and can lead to significant toxicities...
2018: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/29448244/mir-499-ameliorates-podocyte-injury-by-targeting-calcineurin-in-minimal-change-disease
#3
Kaiyue Zhang, Wenjuan Sun, Lai Zhang, Xuefang Xu, Jidong Wang, Yan Hong
BACKGROUND: Podocyte injury is a hallmark of minimal change disease (MCD). Calcineurin inhibitors have been widely used in the current treatment of MCD, and miR-499 may target calcineurin. We aimed to study the function of miR-499 in MCD and test whether miR-499 delivery can improve MCD. METHODS: An MCD mouse model was generated using puromycin aminonucleoside (PAN). MiR-499 was delivered using lentiviruses. Biochemical indicators including serum albumin, triglyceride, cholesterol, and 24-h urine protein were determined...
February 15, 2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29446486/interleukin-17a-participates-in-podocyte-injury-by-inducing-il-1%C3%AE-secretion-through-ros-nlrp3-inflammasome-caspase-1-pathway
#4
Junli Yan, Yao Li, Haiping Yang, Li Zhang, Baohui Yang, Mo Wang, Qiu Li
Studies show that the Th17/IL-17A axis plays an important role in the pathogenesis of kidney diseases. Previously, we also showed that IL-17A may play a role in the pathogenesis of primary nephrotic syndrome; however, the underlying mechanism(s) is unclear. The aim of this study was to explore the molecular mechanism of IL-17A inducing podocyte injury in vitro. In this study, the NLRP3 inflammsome activation and the morphology of podocytes were detected by western blot and immunofluorescence .The results showed that podocytes persistently expressed IL-17A receptor, and that NLRP3 inflammasome in these cells was activated upon exposure to IL-17A...
February 15, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29446059/the-novel-involvement-of-podocyte-autophagic-activity-in-the-pathogenesis-of-lupus-nephritis
#5
Juan Jin, Meiyu Ye, Li Zhao, Wenli Zou, Wei Shen, Hongjuan Zhang, Jianguang Gong, Qiang He
BACKGROUND: Lupus nephritis (LN) is one of the most common and severe complications in Systemic lupus erythematosus patients, and the mechanism underlining the pathogenesis of LN is still unknown. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In this study, we investigated the role of autophagy in the progression of LN. METHODS: Autophagic activities in podocytes of both LN patients (Class IV and V) and mice were evaluated...
February 15, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29444469/mangiferin-prevents-diabetic-nephropathy-progression-and-protects-podocyte-function-via-autophagy-in-diabetic-rat-glomeruli
#6
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29439807/could-notch-signaling-pathway-be-a-potential-therapeutic-option-in-renal-diseases
#7
Laura Marquez-Exposito, Elena Cantero-Navarro, Carolina Lavoz, Marta Fierro-Fernández, Jonay Poveda, Sandra Rayego-Mateos, Raúl R Rodrigues-Diez, José Luis Morgado-Pascual, Macarena Orejudo, Sergio Mezzano, Marta Ruiz-Ortega
Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells...
February 10, 2018: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/29435202/podocyte-derived-microparticles-promote-proximal-tubule-fibrotic-signaling-via-p38-mapk-and-cd36
#8
Mercedes N Munkonda, Shareef Akbari, Chloe Landry, Suzy Sun, Fengxia Xiao, Maddison Turner, Chet E Holterman, Rania Nasrallah, Richard L Hébert, Christopher R J Kennedy, Dylan Burger
Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100-1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29434805/overexpression-of-heart-type-fatty-acid-binding-protein-enhances-fatty-acid-induced-podocyte-injury
#9
Qing Gao, Alhossain Sarkar, Yizhi Chen, Bo Xu, Xiaojuan Zhu, Yang Yuan, Tianjun Guan
Deregulated lipid metabolism is a characteristic of metabolic diseases including type 2 diabetes and obesity, and likely contributes to podocyte injury and end-stage kidney disease. Heart-type fatty acid binding protein (H-FABP) was reported to be associated with lipid metabolism. The present study investigated whether H-FABP contributes to podocyte homeostasis. Podocytes were transfected by lentiviral vector to construct a cell line which stably overexpressed H-FABP. Small interfering RNA capable of effectively silencing H-FABP was introduced into podocytes to construct a cell line with H-FABP knockdown...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29429961/generation-of-functioning-nephrons-by-implanting-human-pluripotent-stem-cell-derived-kidney-progenitors
#10
Ioannis Bantounas, Parisa Ranjzad, Faris Tengku, Edina Silajdžić, Duncan Forster, Marie-Claude Asselin, Philip Lewis, Rachel Lennon, Antonius Plagge, Qi Wang, Adrian S Woolf, Susan J Kimber
Human pluripotent stem cells (hPSCs) hold great promise for understanding kidney development and disease. We reproducibly differentiated three genetically distinct wild-type hPSC lines to kidney precursors that underwent rudimentary morphogenesis in vitro. They expressed nephron and collecting duct lineage marker genes, several of which are mutated in human kidney disease. Lentiviral-transduced hPSCs expressing reporter genes differentiated similarly to controls in vitro. Kidney progenitors were subcutaneously implanted into immunodeficient mice...
February 7, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29428904/developmental-disorder-of-podocytes-and-the-related-renal-diseases
#11
Ya-Nan Zhu, Ying Ao, Bin Li, Yang Wan, Hui Wang
Podocyte is one of the main components of glomerular filtration barrier in the kidney; the loss or dysfunction of podocyte could impair the functions of glomerular filtration barrier, leading to development of various renal diseases. Podocyte is a terminally differentiated cell, and thus does not possess any proliferative properties. Accordingly, its number and contribution to renal function are initially determined by its normal development. Information from the literature and results of our research indicate that genetic factors or prenatal adverse environment could cause developmental retardation of podocytes, thereby suggesting the potential fetal developmental origin(s) of kidney diseases, and involvement of epigenetic mechanisms in the regulation of key genes in podocyte development...
February 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29422652/rage-aptamer-attenuates-deoxycorticosterone-acetate-salt-induced-renal-injury-in-mice
#12
Kensei Taguchi, Sho-Ichi Yamagishi, Miyuki Yokoro, Sakuya Ito, Goh Kodama, Yusuke Kaida, Yosuke Nakayama, Ryotaro Ando, Nana Yamada-Obara, Katsuhiko Asanuma, Takanori Matsui, Yuichiro Higashimoto, Craig R Brooks, Seiji Ueda, Seiya Okuda, Kei Fukami
The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE-RAGE axis and MR system in kidney derangement remains unclear. We screened DNA-aptamer directed against RAGE (RAGE-apt) in vitro and examined its effects on renal injury in uninephrectomized deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mice...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29415466/the-role-of-trio-a-rho-guanine-nucleotide-exchange-factor-in-glomerular-podocytes
#13
Mirela Maier, Cindy Baldwin, Lamine Aoudjit, Tomoko Takano
Nephrotic syndrome is a kidney disease featured by heavy proteinuria. It is caused by injury to the specialized epithelial cells called "podocytes" within the filtration unit of the kidney, glomerulus. Previous studies showed that hyperactivation of the RhoGTPase, Rac1, in podocytes causes podocyte injury and glomerulosclerosis (accumulation of extracellular matrix in the glomerulus). However, the mechanism by which Rac1 is activated during podocyte injury is unknown. Trio is a guanine nucleotide exchange factor (GEF) known to activate Rac1...
February 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29406442/genetic-risk-of-apol1-and-kidney-disease-in-children-and-young-adults-of-african-ancestry
#14
Kimberly J Reidy, Rebecca Hjorten, Rulan S Parekh
PURPOSE OF REVIEW: Understanding the genetic risk of APOL1 in children and young adults is important given the lifetime risk of hypertension and kidney disease among children of African descent. We review recent epidemiologic and biologic findings on the effects of APOL1 and kidney disease. RECENT FINDINGS: APOL1 in children and young adults is associated with hypertension, albuminuria and more rapid decline in kidney function and progression to end-stage kidney disease, especially among those with glomerular causes of kidney disease, and those affected by sickle cell disease or HIV...
February 5, 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29398135/activation-of-podocyte-notch-mediates-early-wt1-glomerulopathy
#15
Rowan I Asfahani, Mona M Tahoun, Eve V Miller-Hodges, Jack Bellerby, Alex K Virasami, Robert D Sampson, Dale Moulding, Neil J Sebire, Peter Hohenstein, Peter J Scambler, Aoife M Waters
The Wilms' tumor suppressor gene, WT1, encodes a zinc finger protein that regulates podocyte development and is highly expressed in mature podocytes. Mutations in the WT1 gene are associated with the development of renal failure due to the formation of scar tissue within glomeruli, the mechanisms of which are poorly understood. Here, we used a tamoxifen-based CRE-LoxP system to induce deletion of Wt1 in adult mice to investigate the mechanisms underlying evolution of glomerulosclerosis. Podocyte apoptosis was evident as early as the fourth day post-induction and increased during disease progression, supporting a role for Wt1 in mature podocyte survival...
February 2, 2018: Kidney International
https://www.readbyqxmd.com/read/29395482/podocyte-infolding-glomerulopathy-pig-in-a-patient-with-undifferentiated-connective-tissue-disease-a-case%C3%A2-report
#16
Smita Mary Matthai, Anjali Mohapatra, Ashish J Mathew, Sanjeet Roy, Santosh Varughese, Debashish Danda, Veerasamy Tamilarasi
Podocyte infolding glomerulopathy (PIG) is a recently described pathologic entity characterized by diffuse podocyte infolding into the glomerular basement membrane (GBM) associated with ultrastructurally demonstrable microspherular aggregates. The clinical features, significance, and pathogenesis of this condition are still not well delineated because only a few cases have been documented to date, all from Japan. We report a case of PIG associated with undifferentiated connective tissue disease in an Indian woman who presented with nephrotic syndrome while undergoing treatment for an autoimmune disorder...
January 27, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29393270/vascular-endothelial-growth-factor-a165b-restores-normal-glomerular-water-permeability-in-a-diphtheria-toxin-mouse-model-of-glomerular-injury
#17
Megan Stevens, Christopher R Neal, Andrew H J Salmon, David O Bates, Steven J Harper, Sebastian Oltean
BACKGROUND/AIMS: Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon binding to hDTR it ultimately leads to cell death. We used a podocyte-specific hDTR expressing (Pod-DTR) mouse to assess the anti-permeability and cyto-protective effects of the splice isoform vascular endothelial growth factor (VEGF-A165b). METHODS: The Pod-DTR mouse was crossed with a mouse that over-expressed VEGF-A165b specifically in the podocytes (Neph-VEGF-A165b)...
January 26, 2018: Nephron
https://www.readbyqxmd.com/read/29383936/novel-ras-inhibitors-poricoic-acid-zg-and-poricoic-acid-zh-attenuate-renal-fibrosis-via-wnt-%C3%AE-catenin-pathway-and-targeted-phosphorylation-smad3-signaling
#18
Ming Wang, Dan-Qian Chen, Lin Chen, Hui Zhao, Dan Liu, Zhi-Hao Zhang, Nosratola D Vaziri, Yan Guo, Ying-Yong Zhao, Gang Cao
Renal fibrosis is a common endpoint of the progression of chronic kidney disease (CKD). Suppressing the development and progression of renal fibrosis is essential in the treatment of kidney disease. Our previous study demonstrated that the ethyl acetate extract of the surface layer of Poria cocos exhibited beneficial anti-tubulointerstitial fibrosis. In this study, we isolated new diterpene (PZF) and triterpenes (PZG and PZH) and examined their anti-fibrotic effect. TGF-β1 upregulated the collagen I protein expression in HK-2 cells and PZG and PZH treatment significantly inhibited the upregulated collagen I expression (TGF group 0...
January 31, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29380411/electron-microscopy-of-drosophila-garland-cell-nephrocytes-optimal-preparation-immunostaining-and-stem-tomography
#19
Florian Hochapfel, Lucia Denk, Christine Maaßen, Yulia Zaytseva, Reinhard Rachel, Ralph Witzgall, Michael P Krahn
Due to its structural and molecular similarities to mammalian podocytes, the Drosophila nephrocyte emerged as a model system to study podocyte development and -associated diseases. Similar to podocytes, nephrocytes establish a slit diaphragm between "foot process-like" structures in order to filtrate the hemolymph. One major obstacle in nephrocyte research is the distinct visualization of this subcellular structure to assess its integrity. Therefore, we developed a specialized dissection and fixation protocol, including high pressure freezing and freeze substitution techniques, to improve the preservation of the intricate ultrastructural details necessary for electron microscopic assessment...
January 29, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29378953/disease-causing-mutation-in-%C3%AE-actinin-4-promotes-podocyte-detachment-through-maladaptation-to-periodic-stretch
#20
Di Feng, Jacob Notbohm, Ava Benjamin, Shijie He, Minxian Wang, Lay-Hong Ang, Minaspi Bantawa, Mehdi Bouzid, Emanuela Del Gado, Ramaswamy Krishnan, Martin R Pollak
α-Actinin-4 (ACTN4) bundles and cross-links actin filaments to confer mechanical resilience to the reconstituted actin network. How this resilience is built and dynamically regulated in the podocyte, and the cause of its failure in ACTN4 mutation-associated focal segmental glomerulosclerosis (FSGS), remains poorly defined. Using primary podocytes isolated from wild-type (WT) and FSGS-causing point mutant Actn4 knockin mice, we report responses to periodic stretch. While WT cells largely maintained their F-actin cytoskeleton and contraction, mutant cells developed extensive and irrecoverable reductions in these same properties...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
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