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https://www.readbyqxmd.com/read/29227285/shifts-in-podocyte-histone-h3k27me3-regulate-mouse-and-human-glomerular-disease
#1
Syamantak Majumder, Karina Thieme, Sri N Batchu, Tamadher A Alghamdi, Bridgit B Bowskill, M Golam Kabir, Youan Liu, Suzanne L Advani, Kathryn E White, Laurette Geldenhuys, Karthik K Tennankore, Penelope Poyah, Ferhan S Siddiqi, Andrew Advani
Histone protein modifications control fate determination during normal development and dedifferentiation during disease. Here, we set out to determine the extent to which dynamic changes to histones affect the differentiated phenotype of ordinarily quiescent adult glomerular podocytes. To do this, we examined the consequences of shifting the balance of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark in podocytes. Adriamycin nephrotoxicity and subtotal nephrectomy (SNx) studies indicated that deletion of the histone methylating enzyme EZH2 from podocytes decreased H3K27me3 levels and sensitized mice to glomerular disease...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29224013/response-of-renal-podocytes-to-excessive-hydrostatic-pressure-a-pathophysiologic-cascade-in-a-malignant-hypertension-model
#2
Ramzia Abu Hamad, Sylvia Berman, Yafit Hachmo, Moshe Stark, Fadia Hasan, Keren Doenyas-Barak, Shai Efrati
BACKGROUND/AIMS: Renal injuries induced by increased intra-glomerular pressure coincide with podocyte detachment from the glomerular basement membrane (GBM). In previous studies, it was demonstrated that mesangial cells have a crucial role in the pathogenesis of malignant hypertension. However, the exact pathophysiological cascade responsible for podocyte detachment and its relationship with mesangial cells has not been fully elucidated yet and this was the aim of the current study. METHODS: Rat renal mesangial or podocytes were exposed to high hydrostatic pressure in an in-vitro model of malignant hypertension...
December 7, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29223856/modulation-of-glutathione-peroxidase-activity-by-age-dependent-carbonylation-in-glomeruli-of-diabetic-mice
#3
Tanja Wiedenmann, Nadine Dietrich, Thomas Fleming, Sandro Altamura, Leo E Deelman, Rob H Henning, Martina U Muckenthaler, Peter P Nawroth, Hans-Peter Hammes, Andreas H Wagner, Markus Hecker
AIMS: Low levels of reactive oxygen species and resulting oxidative protein modifications may play a beneficial role in cellular function under stress conditions. Here we studied the influence of age-dependent protein carbonylation on expression and activity of the anti-oxidative selenoenzyme glutathione peroxidase (GPx) in insulin-deficient Ins2Akita mice and type 2 diabetic obese db/db mice in context of diabetic nephropathy. METHODS: Protein carbonylation, GPx expression and activity were examined in kidney tissue and lysates by common histological and protein biochemical methods...
November 22, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29218112/triptolide-protects-podocytes-from-tgf-%C3%AE-induced-injury-by-preventing-mir-30-downregulation
#4
Qianqian Yang, Mengjie Sun, Ying Chen, Yuqiu Lu, Yuting Ye, Hui Song, Xiaodong Xu, Shaolin Shi, Jinquan Wang
Triptolide is known to have a strong anti-proteinuric effect through direct protection of podocytes from injury and is used to treat glomerular diseases. However, the mechanism underlying its protective effect on podocytes remains elusive. MiR-30 family has recently been shown to be essential for structural and functional homeostasis of podocytes but is downregulated by injurious factors, leading to podocyte injury. In the present study, we explore whether Triptolide protects podocytes through preventing miR-30 downregulation...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29217578/a-small-molecule-inhibitor-of-trpc5-ion-channels-suppresses-progressive-kidney-disease-in-animal-models
#5
Yiming Zhou, Philip Castonguay, Eriene-Heidi Sidhom, Abbe R Clark, Moran Dvela-Levitt, Sookyung Kim, Jonas Sieber, Nicolas Wieder, Ji Yong Jung, Svetlana Andreeva, Jana Reichardt, Frank Dubois, Sigrid C Hoffmann, John M Basgen, Mónica S Montesinos, Astrid Weins, Ashley C Johnson, Eric S Lander, Michael R Garrett, Corey R Hopkins, Anna Greka
Progressive kidney diseases are often associated with scarring of the kidney's filtration unit, a condition called focal segmental glomerulosclerosis (FSGS). This scarring is due to loss of podocytes, cells critical for glomerular filtration, and leads to proteinuria and kidney failure. Inherited forms of FSGS are caused by Rac1-activating mutations, and Rac1 induces TRPC5 ion channel activity and cytoskeletal remodeling in podocytes. Whether TRPC5 activity mediates FSGS onset and progression is unknown. We identified a small molecule, AC1903, that specifically blocks TRPC5 channel activity in glomeruli of proteinuric rats...
December 8, 2017: Science
https://www.readbyqxmd.com/read/29214442/shiga-toxin-triggers-endothelial-and-podocyte-injury-the-role-of-complement-activation
#6
REVIEW
Carlamaria Zoja, Simona Buelli, Marina Morigi
Shiga toxin (Stx)-producing Escherichia coli (STEC) is the offending agent in post-diarrhea-associated hemolytic uremic syndrome (HUS), a disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney failure, with thrombi occluding the renal microvasculature. Endothelial dysfunction has been recognized as the trigger event in the development of microangiopathic processes. Glomerular endothelial cells are susceptible to the toxic effects of Stxs that, via nuclear factor kappa B (NF-κB) activation, induce the expression of genes encoding for adhesion molecules and chemokines, culminating in leukocyte adhesion and platelet thrombus formation on the activated endothelium...
December 6, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29214160/mir-217-is-a-useful-diagnostic-biomarker-and-regulates-human-podocyte-cells-apoptosis-via-targeting-tnfsf11-in-membranous-nephropathy
#7
Jing Li, Bin Liu, Hen Xue, Qiao Qiao Zhou, Ling Peng
Background: MicroRNAs have recently been verified as useful diagnostic biomarkers in various diseases. In this study, we investigated whether miR-217 is a useful diagnostic biomarker and the possible pathological mechanism of miR-217 in this disease. Methods: Patients with focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and diabetic nephropathy (DN) and control patients were enrolled in this study. The miR-217 inhibitor and mimics were transfected into human podocyte cells to investigate the pathological mechanism of miR-217 in this disease...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29212948/elevated-urinary-creld2-is-associated-with-endoplasmic-reticulum-stress-mediated-kidney-disease
#8
Yeawon Kim, Sun-Ji Park, Scott R Manson, Carlos Af Molina, Kendrah Kidd, Heather Thiessen-Philbrook, Rebecca J Perry, Helen Liapis, Stanislav Kmoch, Chirag R Parikh, Anthony J Bleyer, Ying Maggie Chen
ER stress has emerged as a signaling platform underlying the pathogenesis of various kidney diseases. Thus, there is an urgent need to develop ER stress biomarkers in the incipient stages of ER stress-mediated kidney disease, when a kidney biopsy is not yet clinically indicated, for early therapeutic intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly identified protein that is induced and secreted under ER stress. For the first time to our knowledge, we demonstrate that CRELD2 can serve as a sensitive urinary biomarker for detecting ER stress in podocytes or renal tubular cells in murine models of podocyte ER stress-induced nephrotic syndrome and tunicamycin- or ischemia-reperfusion-induced acute kidney injury (AKI), respectively...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29208058/low-protein-diet-supplemented-with-ketoacids-delays-the-progression-of-diabetic-nephropathy-by-inhibiting-oxidative-stress-in-the-kkay-mice-model
#9
Dongmei Liu, Ming Wu, Lin Li, Xiang Gao, Bo Yang, Shuqin Mei, Lili Fu, Changlin Mei
Diabetic nephropathy (DN) is a major cause of chronic kidney disease. We aimed to investigate the effect of the low-protein diets (LPD) supplemented with ketoacids (LPD+KA) in KKAy mice, an early type 2 DN model. KKAy mice were treated with normal protein diet (NPD), LPD or LPD+KA from 12 to 24 weeks of age. A period of 12-week treatment with LPD significantly reduced albuminuria as compared with that observed after NPD treatment. Treatment with LPD+KA further reduced albuminuria as compared with that observed with LPD treatment alone...
December 6, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/29207635/socs2-overexpression-alleviates-diabetic-nephropathy-in-rats-by-inhibiting-the-tlr4-nf-%C3%AE%C2%BAb-pathway
#10
Suxia Yang, Junwei Zhang, Shiying Wang, Xinxin Zhao, Jun Shi
Suppressor of cytokine signaling 2 (SOCS2) was reported to be involved in the development of Diabetic Nephropathy (DN). However, its underlying mechanism remains undefined. Western blot was carried out to determine the expressions of SOCS2, Toll-like receptors 4 (TLR4) and nuclear factor kappa B (NF-κB) pathway-related proteins in DN patients, streptozotocin (STZ)-induced DN rats and high glucose (HG)-stimulated podocytes. The effects of SOCS2 overexpression on renal injury, the inflammatory cytokines production, renal pathological changes, apoptosis and the TLR4/NF-κB pathway in DN rats or HG-stimulated podocytes were investigated...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207011/astragaloside-iv-prevents-kidney-injury-caused-by-iatrogenic-hyperinsulinemia-in-a-streptozotocin%C3%A2-induced-diabetic-rat-model
#11
Ke-Qiang He, Wei-Zu Li, Xiao-Qing Chai, Yan-Yan Yin, Yan Jiang, Wei-Ping Li
Diabetic patients are able to manage their blood glucose with exogenous insulin but, ultimately, remain at risk of diabetic nephropathy (DN). Long‑term use of insulin may lead to iatrogenic hyperinsulinemia, which has been suggested to cause kidney injury. However, there are no effective interventions for iatrogenic hyperinsulinemia leading to kidney damage. In the present paper, the hypothesis that astragaloside IV (AS‑IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bunge, may prevent DN in iatrogenic hyperinsulinemic diabetic rats through antioxidative and anti‑inflammatory mechanisms was investigated...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29205354/podocytes-are-new-cellular-targets-of-hemoglobin-mediated-renal-damage
#12
Alfonso Rubio-Navarro, Maria Dolores Sanchez-Niño, Melania Guerrero-Hue, Cristina García-Caballero, Eduardo Gutiérrez, Claudia Yuste, Ángel Sevillano, Manuel Praga, Javier Egea, Elena Román, Pablo Cannata, Rosa Ortega, Isabel Cortegano, Belén de Andrés, María Luisa Gaspar, Susana Cadenas, Alberto Ortiz, Jesús Egido, Juan Antonio Moreno
Recurrent and massive intravascular hemolysis induces proteinuria, glomerulosclerosis and progressive impairment of renal function, suggesting podocyte injury. However, the effects of hemoglobin (Hb) on podocytes remain unexplored. Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin-cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway and altered podocyte morphology, with decreased expressionof the slit diaphragm proteins nephrin and synaptopodin...
December 4, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29198839/sox9-activation-is-involved-in-tubule-repair-after-unilateral-partial-nephrectomy
#13
Qiwang Ma, Yujia Wang, Wei Zuo
AIMS: Tubule repair has been noticed after kidney tissue damage, however the cellular mechanism behind remains unclear. Here we successfully constructed a mouse unilateral partial nephrectomy model mimicking renal carcinoma surgery, and further investigated whether this procedure triggered regenerative action. MAIN METHODS: We used the unilateral partial nephrectomy model to study kidney repair. Kidney function after nephrectomy was measured using creatinine and urea nitrogen assay kit...
November 30, 2017: Life Sciences
https://www.readbyqxmd.com/read/29198665/isolated-crystalloid-podocytopathy-with-focal-segmental-glomerulosclerosis-in-renal-allograft-an-unusual-presentation-of-post-transplant-monoclonal-gammopathy-of-renal-significance-a-case-report
#14
A-H Yang, C-C Loong, N-C Lin, C-Y Yang
BACKGROUND: Monoclonal gammopathy of renal significance denotes a spectrum of hematologic disorders that cause direct or indirect renal damage. CASE PRESENTATION: A 51-year-old man had received a living-donor kidney transplant from his wife in 2008. He had gradual increased proteinuria 4 years later. His renal biopsy results revealed cytoplasmic crystalloid inclusions in the podocytes. No crystalloid inclusion was found in other renal cells. Despite that immunofluorescent examination failed to show light-chain deposition, the serum immuno-electrophoresis revealed monoclonal immunoglobulin-Gκ...
December 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29192064/fyn-binding-protein-adap-supports-actin-organization-in-podocytes
#15
Zhenzhen Wu, Natalya A Blessing, Jeffrey S Simske, Leslie A Bruggeman
The renal podocyte is central to the filtration function of the kidney that is dependent on maintaining both highly organized, branched cell structures forming foot processes, and a unique cell-cell junction, the slit diaphragm. Our recent studies investigating the developmental formation of the slit diaphragm identified a novel claudin family tetraspannin, TM4SF10, which is a binding partner for ADAP (also known as Fyn binding protein Fyb). To investigate the role of ADAP in podocyte function in relation to Fyn and TM4SF10, we examined ADAP knockout (KO) mice and podocytes...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29191133/focal-segmental-glomerulosclerosis-in-related-miniature-schnauzer-dogs
#16
Wilson Yau, Lisa Mausbach, Meryl P Littman, Rachel E Cianciolo, Cathy A Brown
Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs in particular. This study describes the morphologic features present in the kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS, characterized by solidification of portions of the capillary tuft, affected 32% to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in older dogs...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/29190634/focal-segmental-glomerulosclerosis-associated-with-chronic-progressive-external-ophthalmoplegia-and-mitochondrial-dna-a3243g-mutation
#17
Kaori Narumi, Eikan Mishima, Yukako Akiyama, Tetsuro Matsuhashi, Takashi Nakamichi, Kiyomi Kisu, Shuhei Nishiyama, Hajime Ikenouchi, Akio Kikuchi, Rumiko Izumi, Mariko Miyazaki, Takaaki Abe, Hiroshi Sato, Sadayoshi Ito
Focal segmental glomerulosclerosis (FSGS) is caused by various etiologies, with mitochondrial dysfunction being one of the causes. FSGS is known to be associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), which is a subclass of mitochondrial disease. However, it has rarely been reported in other mitochondrial disease subclasses. Here, we reported a 20-year-old man diagnosed with FSGS associated with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA (mtDNA) 3243A>G mutation...
November 30, 2017: Nephron
https://www.readbyqxmd.com/read/29187370/ste20-like-kinase-slk-a-novel-mediator-of-podocyte-integrity
#18
Andrey V Cybulsky, Joan Papillon, Julie Guillemette, Natalya Belkina, Genaro Patino-Lopez, Elena Torban
SLK is essential for embryonic development, and may play a key role in wound healing, tumor growth and metastasis. Expression and activation of SLK is increased in kidney development and during recovery from ischemic acute kidney injury. Overexpression of SLK in glomerular epithelial cells/podocytes in vivo induces injury and proteinuria. Conversely, reduced SLK expression leads to abnormalities in cell adhesion, spreading, and motility. Tight regulation of SLK expression thus may be critical for normal renal structure and function...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29186855/translational-aspects-of-sphingolipid-metabolism-in-renal-disorders
#19
REVIEW
Alaa Abou Daher, Tatiana El Jalkh, Assaad A Eid, Alessia Fornoni, Brian Marples, Youssef H Zeidan
Sphingolipids, long thought to be passive components of biological membranes with merely a structural role, have proved throughout the past decade to be major players in the pathogenesis of many human diseases. The study and characterization of several genetic disorders like Fabry's and Tay Sachs, where sphingolipid metabolism is disrupted, leading to a systemic array of clinical symptoms, have indeed helped elucidate and appreciate the importance of sphingolipids and their metabolites as active signaling molecules...
November 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29184126/genetic-and-pharmacological-inhibition-of-microrna-92a-maintains-podocyte-cell-cycle-quiescence-and-limits-crescentic-glomerulonephritis
#20
Carole Henique, Guillaume Bollée, Xavier Loyer, Florian Grahammer, Neeraj Dhaun, Marine Camus, Julien Vernerey, Léa Guyonnet, François Gaillard, Hélène Lazareth, Charlotte Meyer, Imane Bensaada, Luc Legrès, Takashi Satoh, Shizuo Akira, Patrick Bruneval, Stefanie Dimmeler, Alain Tedgui, Alexandre Karras, Eric Thervet, Dominique Nochy, Tobias B Huber, Laurent Mesnard, Olivia Lenoir, Pierre-Louis Tharaux
Crescentic rapidly progressive glomerulonephritis (RPGN) represents the most aggressive form of acquired glomerular disease. While most therapeutic approaches involve potentially toxic immunosuppressive strategies, the pathophysiology remains incompletely understood. Podocytes are glomerular epithelial cells that are normally growth-arrested because of the expression of cyclin-dependent kinase (CDK) inhibitors. An exception is in RPGN where podocytes undergo a deregulation of their differentiated phenotype and proliferate...
November 28, 2017: Nature Communications
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