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https://www.readbyqxmd.com/read/28228401/wolf-hirschhorn-syndrome-candidate-1-like-1-epigenetically-regulates-nephrin-gene-expression
#1
Yugo Ito, Kan Katayama, Yukino Nishibori, Yoshihiro Akimoto, Akihiko Kudo, Ryota Kurayama, Ichiro Hada, Shohei Takahashi, Toru Kimura, Toshiyuki Fukutomi, Tomohisa Katada, Junichi Suehiro, Olga Beltcheva, Karl Tryggvason, Kunimasa Yan
Altered expression of nephrin underlies the pathophysiology of proteinuria in both congenital and acquired nephrotic syndrome. However, the epigenetic mechanisms of nephrin gene regulation remain elusive. Here, we show that Wolf-Hirschhorn syndrome candidate 1-like 1 long form (WHSC1L1-L) is a novel epigenetic modifier of nephrin gene regulation. WHSC1L1-L was associated with histone H3K4 and H3K36 in human embryonic kidney cells. WHSC1L1-L gene was expressed in the podocytes and functional protein product was detected in these cells...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28218578/bone-marrow-derived-mesenchymal-stem-cells-ameliorate-nephrosis-through-repair-of-impaired-podocytes
#2
Yi Chen, Jun Chen, Jianxin Wan, Na Gao, Jiong Cui, Danyu You, Zhenhuan Zou
PURPOSE: The purpose of this study was to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSC) on podocytes of puromycin amino nuclear glucoside (PAN) -induced nephrosis in mice. METHODS: Mice were randomly divided into Control, PAN and BMSC groups. Mice were injected with PAN (0.5 mg/g weight) via the tail vein. The 24-h urinary protein was obtained after modelling, and urinary protein excretion was determined. The blood and kidney specimens were isolated after the tenth day of modelling...
February 19, 2017: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/28199971/association-and-interaction-effects-of-alzheimer-s-disease-associated-genes-and-lifestyle-on-cognitive-aging-in-older-adults-in-a-taiwanese-population
#3
Eugene Lin, Shih-Jen Tsai, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao
Genome-wide association studies and meta-analyses implicated that increased risk of developing Alzheimer's diseases (AD) has been associated with the ABCA7, APOE, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB1, HLA-DRB4, INPP5D, MEF2C, MS4A4A, MS4A4E, MS4A6E, NME8, PICALM, PLD3, PTK2B, RIN3, SLC24A4, SORL1, and ZCWPW1 genes. In this study, we assessed whether single nucleotide polymorphisms (SNPs) within these 27 AD-associatedgenes are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28163747/tangzhiqing-granules-alleviate-podocyte-epithelial-mesenchymal-transition-in-kidney-of-diabetic-rats
#4
Haiyan Xu, Xu Wang, Mingming Liu, Xueyuan He
This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28123638/nicousamide-protects-kidney-podocyte-by-inhibiting-the-tgf%C3%AE-receptor-ii-phosphorylation-and-age-rage-signaling
#5
Sen Zhang, Dongjie Wang, Nina Xue, Fangfang Lai, Ming Ji, Jing Jin, Xiaoguang Chen
Nicousamide, a clinical phase II renal protective new drug, has been demonstrated to have renal protective effect on diabetic nephropathy (DN) by experimental animal model. Its known molecular mechanisms include AGE formation blocking and moderately decreasing the blood pressure. Nicousamide shows potential on attenuating albuminuria, thereby suggests it might have protective effect on podocytes. The aim of present study was to investigate whether nicousamide could protect integrity of podocytes, and further its protection mechanisms...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/27993940/bin1-and-cd2ap-polarize-a%C3%AE-generation-in-neurons
#6
Ragna Sannerud, Wim Annaert
No abstract text is available yet for this article.
January 2017: EMBO Reports
https://www.readbyqxmd.com/read/27895104/bin1-and-cd2ap-polarise-the-endocytic-generation-of-beta-amyloid
#7
Florent Ubelmann, Tatiana Burrinha, Laura Salavessa, Ricardo Gomes, Cláudio Ferreira, Nuno Moreno, Cláudia Guimas Almeida
The mechanisms driving pathological beta-amyloid (Aβ) generation in late-onset Alzheimer's disease (AD) are unclear. Two late-onset AD risk factors, Bin1 and CD2AP, are regulators of endocytic trafficking, but it is unclear how their endocytic function regulates Aβ generation in neurons. We identify a novel neuron-specific polarisation of Aβ generation controlled by Bin1 and CD2AP We discover that Bin1 and CD2AP control Aβ generation in axonal and dendritic early endosomes, respectively. Both Bin1 loss of function and CD2AP loss of function raise Aβ generation by increasing APP and BACE1 convergence in early endosomes, however via distinct sorting events...
January 2017: EMBO Reports
https://www.readbyqxmd.com/read/27883225/computational-screening-and-exploration-of-disease-associated-genes-in-alzheimer-s-disease
#8
Salma Jamal, Sukriti Goyal, Asheesh Shanker, Abhinav Grover
Alzheimer's is a neurodegenerative disease affecting large populations worldwide characterized mainly by progressive loss of memory along with various other symptoms. The foremost cause of the disease is still unclear, however various mechanisms have been proposed to cause the disease that include amyloid hypothesis, tau hypothesis, and cholinergic hypothesis in addition to genetic factors. Various genes have been known to be involved which are APOE, PSEN1, PSEN2, and APP among others. In the present study, we have used computational methods to examine the pathogenic effects of non-synonymous single nucleotide polymorphisms (SNPs) associated with ABCA7, CR1, MS4A6A, CD2AP, PSEN1, PSEN2, and APP genes...
November 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27849641/genetic-comparison-of-symptomatic-and-asymptomatic-persons-with-alzheimer-disease-neuropathology
#9
Sarah E Monsell, Charles Mock, David W Fardo, Sarah Bertelsen, Nigel J Cairns, Catherine M Roe, Sally R Ellingson, John C Morris, Alison M Goate, Walter A Kukull
OBJECTIVE: The objective was to determine whether symptomatic and asymptomatic persons with Alzheimer's disease (AD) neuropathology have different allele counts for single-nucleotide polymorphisms that have been associated with clinical late-onset AD. METHODS: Data came from the National Alzheimer's Coordinating Center Uniform Data Set and Neuropathology Data Set, and the Alzheimer's Disease Genetics Consortium (ADGC). Participants had low to high AD neuropathologic change...
November 15, 2016: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/27765817/adaptor-protein-cd2ap-and-l-type-lectin-lman2-regulate-exosome-cargo-protein-trafficking-through-the-golgi-complex
#10
Sang-Ho Kwon, Sekyung Oh, Marisa Nacke, Keith E Mostov, Joshua H Lipschutz
Exosomes, 40-150-nm extracellular vesicles, transport biological macromolecules that mediate intercellular communications. Although exosomes are known to originate from maturation of endosomes into multivesicular endosomes (also known as multivesicular bodies) with subsequent fusion of the multivesicular endosomes with the plasma membrane, it remains unclear how cargos are selected for exosomal release. Using an inducible expression system for the exosome cargo protein GPRC5B and following its trafficking trajectory, we show here that newly synthesized GPRC5B protein accumulates in the Golgi complex prior to its release into exosomes...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27590856/cd2-associated-protein-phosphoinositide-3-kinase-signaling-has-a-preventive-role-in-angiotensin-ii-induced-podocyte-apoptosis
#11
Hye-Young Park, Su-Bin Seong, Seo-Yun Min, Tae-Sun Ha
Angiotensin II (Ang II) works as a paracrine or autocrine cytokine agent to regulate renal functions and promotes podocytes dysfunction directly or indirectly, causing proteinuria. The glomerular slit diaphragm (SD) serves as a size-selective barrier and is linked to the actin-based cytoskeleton by adaptor proteins, including CD2-associated protein (CD2AP). Therefore, damages to CD2AP affect not only the function of the SD, but also directly disrupt the podocyte cytoskeleton, leading to proteinuria. In addition, CD2AP can facilitate the nephrin-induced phosphoinositide 3-kinase (PI3-K)/Akt signaling, which protects podocytes from apoptosis...
October 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27573339/novel-nphs2-variant-in-patients-with-familial-steroid-resistant-nephrotic-syndrome-with-early-onset-slow-progression-and-dominant-inheritance-pattern
#12
Maija Suvanto, Jaakko Patrakka, Timo Jahnukainen, Pia-Maria Sjöström, Matti Nuutinen, Pekka Arikoski, Janne Kataja, Marjo Kestilä, Hannu Jalanko
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a common cause of end-stage renal disease in children but also occurs as an adult-onset condition. In a subset of SRNS patients, pathogenic variants are found in genes coding for podocyte foot process proteins. The aim of this study was to define the role of pathogenic variants in Finnish patients with familial and sporadic SRNS. METHODS: We analyzed SRNS-related genes NPHS1, NPHS2, NEPH1, ACTN4, TRPC6, INF2, WT1, CD2AP, LAMB2, and PLCE1 for disease-causing variants using direct sequencing of exons and intron/exon boundaries in all members of a family with dominant SRNS with early onset and slow progression to end-stage renal disease...
August 29, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27539963/adipocytes-play-an-etiological-role-in-the-podocytopathy-of-high-fat-diet-fed-rats
#13
Jinn-Yang Chen, Deng-Yuan Jian, Chih-Chan Lien, Yu-Ting Lin, Ching-Heng Ting, Luen-Kui Chen, Ting-Chia Hsu, Hsuan-Min Huang, Yu-Ting Wu, Tse-Ting Kuan, Yu-Wen Chao, Liang-Yi Wu, Seng-Wong Huang, Chi-Chang Juan
Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes...
November 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27461219/association-of-kidney-structure-related-gene-variants-with-type-2-diabetes-attributed-end-stage-kidney-disease-in-african-americans
#14
Meijian Guan, Jun Ma, Jacob M Keaton, Latchezar Dimitrov, Poorva Mudgal, Mary Stromberg, Jason A Bonomo, Pamela J Hicks, Barry I Freedman, Donald W Bowden, Maggie C Y Ng
African Americans (AAs) are at higher risk for developing end-stage kidney disease (ESKD) compared to European Americans. Genome-wide association studies have identified variants associated with diabetic and non-diabetic kidney diseases. Nephropathy loci, including SLC7A9, UMOD, and SHROOM3, have been implicated in the maintenance of normal glomerular and renal tubular structure and function. Herein, 47 genes important in podocyte, glomerular basement membrane, mesangial cell, mesangial matrix, renal tubular cell, and renal interstitium structure were examined for association with type 2 diabetes (T2D)-attributed ESKD in AAs...
November 2016: Human Genetics
https://www.readbyqxmd.com/read/27441654/tankyrase-inhibition-aggravates-kidney-injury-in-the-absence-of-cd2ap
#15
S Kuusela, H Wang, A A Wasik, H Suleiman, S Lehtonen
Inappropriate activation of the Wnt/β-catenin pathway has been indicated in podocyte dysfunction and injury, and shown to contribute to the development and progression of nephropathy. Tankyrases, multifunctional poly(ADP-ribose) polymerase (PARP) superfamily members with features of both signaling and cytoskeletal proteins, antagonize Wnt/β-catenin signaling. We found that tankyrases interact with CD2-associated protein (CD2AP), a protein essential for kidney ultrafiltration as CD2AP-knockout (CD2AP-/-) mice die of kidney failure at the age of 6-7 weeks...
July 21, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27335373/podocyte-injury-the-role-of-proteinuria-urinary-plasminogen-and-oxidative-stress
#16
Leopoldo Raij, Runxia Tian, Jenny S Wong, John C He, Kirk N Campbell
Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA)...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27289440/abca7-p-g215s-as-potential-protective-factor-for-alzheimer-s-disease
#17
Celeste Sassi, Michael A Nalls, Perry G Ridge, Jesse R Gibbs, Jinhui Ding, Michelle K Lupton, Claire Troakes, Katie Lunnon, Safa Al-Sarraj, Kristelle S Brown, Christopher Medway, Naomi Clement, Jenny Lord, James Turton, Jose Bras, Maria R Almeida, Henne Holstege, Eva Louwersheimer, Wiesje M van der Flier, Philip Scheltens, John C Van Swieten, Isabel Santana, Catarina Oliveira, Kevin Morgan, John F Powell, John S Kauwe, Carlos Cruchaga, Alison M Goate, Andrew B Singleton, Rita Guerreiro, John Hardy
Genome-wide association studies (GWASs) have been effective approaches to dissect common genetic variability underlying complex diseases in a systematic and unbiased way. Recently, GWASs have led to the discovery of over 20 susceptibility loci for Alzheimer's disease (AD). Despite the evidence showing the contribution of these loci to AD pathogenesis, their genetic architecture has not been extensively investigated, leaving the possibility that low frequency and rare coding variants may also occur and contribute to the risk of disease...
October 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27169889/treatment-with-irbesatan-may-improve-slit-diaphragm-alterations-in-rats-with-adriamycin-induced-nephropathy
#18
Na Wang, Ri-bao Wei, Ping Li, Qing-ping Li, Xi Yang, Yue Yang, Meng-jie Huang, Rui Wang, Zhong Yin, Yang Lv, Xiang-mei Chen
OBJECTIVE: The study aimed to evaluate the effects of oral administration of irbesartan in adriamycin-induced nephropathy considering laboratory changes, kidney histology, and expression of proteins related to slit diaphragm and cytoskeleton of the podocyte. METHODS: The animals were divided into control, model, methylprednisolone (MP), and irbesartan groups. The 24-hour urinary protein and biochemical indicators were determined, and renal pathological changes were observed...
April 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27135718/genomics-of-alzheimer-disease-a-review
#19
Roger N Rosenberg, Doris Lambracht-Washington, Gang Yu, Weiming Xia
IMPORTANCE: To provide a comprehensive review of knowledge of the genomics of Alzheimer disease (AD) and DNA amyloid β 42 (Aβ42) vaccination as a potential therapy. OBSERVATIONS: Genotype-phenotype correlations of AD are presented to provide a comprehensive appreciation of the spectrum of disease causation. Alzheimer disease is caused in part by the overproduction and lack of clearance of Aβ protein. Oligomer Aβ, the most toxic species of Aβ, causes direct injury to neurons, accompanied by enhanced neuroinflammation, astrocytosis and gliosis, and eventually neuronal loss...
July 1, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27083281/cystinosin-deficiency-causes-podocyte-damage-and-loss-associated-with-increased-cell-motility
#20
Ekaterina A Ivanova, Fanny O Arcolino, Mohamed A Elmonem, Maria P Rastaldi, Laura Giardino, Elisabeth M Cornelissen, Lambertus P van den Heuvel, Elena N Levtchenko
The involvement of the glomerulus in the pathogenesis of cystinosis, caused by loss-of-function mutations in cystinosin (CTNS, 17p13), is a matter of controversy. Although patients with cystinosis demonstrate glomerular lesions and high-molecular-weight proteinuria starting from an early age, a mouse model of cystinosis develops only signs of proximal tubular dysfunction. Here we studied podocyte damage in patients with cystinosis by analyzing urinary podocyte excretion and by in vitro studies of podocytes deficient in cystinosin...
May 2016: Kidney International
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