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https://www.readbyqxmd.com/read/29746568/the-protective-effect-of-the-ep2-receptor-on-tgf-%C3%AE-1-induced-podocyte-injury-via-the-pi3k-akt-signaling-pathway
#1
Jing Liu, Yi-de Zhang, Xiao-Lan Chen, Xue-Ling Zhu, Xu Chen, Jian-Hua Wu, Nai-Feng Guo
Transforming growth factor β1 (TGF-β1) plays a central role in chronic kidney diseases. TGF-β1 induction causes podocyte injury, which results in proteinuria and renal failure. However, the effect of the prostaglandin E2 /E-prostanoid receptor (EP2) on TGF-β1-induced podocyte injury remains unknown. Previous studies have shown that phosphoinositide 3-OH kinase (PI3K)/Akt is widespread in cells, and is vital for the regulation of cell proliferation, differentiation, apoptosis and metabolism. In this study, we cultured immortalized mouse podocytes in vitro in different groups: control group; TGF-β1 (5ng/ml) group; EP2 agonist Butaprost treatment (10-7, 10-6, or 10-5mol/L) +TGF-β1 group; EP2 antagonist AH6809 treatment (10-7, 10-6, or 10-5mol / L) + TGF-β1 group...
2018: PloS One
https://www.readbyqxmd.com/read/29734372/the-adaptor-molecule-cd2ap-in-cd4-t-cells-modulates-differentiation-of-follicular-helper-t-cells-during-chronic-lcmv-infection
#2
Saravanan Raju, Kohei Kometani, Tomohiro Kurosaki, Andrey S Shaw, Takeshi Egawa
CD4 T cell-mediated help to CD8 T cells and B cells is a critical arm of the adaptive immune system required for control of pathogen infection. CD4 T cells express cytokines and co-stimulatory molecules that support a sustained CD8 T cell response and also enhance generation of protective antibody by germinal center B cells. However, the molecular components that modulate CD4 T cell functions in response to viral infection or vaccine is incompletely understood. Here we demonstrate that inactivation of the signaling adaptor CD2-associated protein (CD2AP) promotes CD4 T cell differentiation towards the follicular helper lineage, leading to enhanced control of viral infection by augmented germinal center response in chronic lymphocytic choriomeningitis virus (LCMV) infection...
May 7, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29729186/cd2-associated-protein-contributes-to-hepatitis-c-virus-propagation-and-steatosis-by-disrupting-insulin-signaling
#3
Huixia Zhang, Chao Zhang, Hong Tang, Shanshan Gao, Fang Sun, Yuan Yang, Weiping Zhou, Yu Hu, Changshu Ke, Yu Wu, Zeyang Ding, Lin Guo, Rongjuan Pei, Xinwen Chen, Man- Sun Sy, Bixiang Zhang, Chaoyang Li
Chronic hepatitis C virus (HCV) infection can result in steatosis, a condition displaying aberrant accumulation of neutral lipid vesicles, the component of lipid droplets (LDs), which are essential for HCV assembly. However, the interplays between HCV infection and steatosis remain unclear. Here, we show that HCV infected cells have higher levels of CD2-associated protein (CD2AP), which plays two distinct, yet tightly-linked roles in HCV pathogenesis: elevated CD2AP binding to NS5A and participating in the transport of NS5A to LDs to facilitate viral assembly; up-regulated CD2AP also interacting with Casitas B-lineage Lymphoma (b) (Cbl/Cbl-b) E3 ligases to degrade insulin receptor substrate 1 (IRS1), which in turn disrupts insulin signaling and increases LDs accumulation thru the IRS1-Akt-AMPK-hormone sensitive lipase (HSL) signaling axis to accommodate viral assembly...
May 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29704630/knockdown-of-nup160-inhibits-cell-proliferation-induces-apoptosis-autophagy-and-cell-migration-and-alters-the-expression-and-localization-of-podocyte-associated-molecules-in-mouse-podocytes
#4
Ping Wang, Feng Zhao, Xiaojing Nie, Jiewei Liu, Zihua Yu
Genetic mutations in dozens of monogenic genes can lead to serious podocyte dysfunction, which is a major cause of steroid-resistant nephrotic syndrome (SRNS). The NUP160 gene is expressed in both human kidney and mouse kidney. However, whether knockdown of NUP160 impairs podocytes has not yet been established. Therefore, we knocked down NUP160 by targeted short hairpin RNA (shRNA) in conditionally immortalized mouse podocytes and observed the effect of NUP160 knockdown on the proliferation, apoptosis, autophagy and cell migration of podocytes...
April 25, 2018: Gene
https://www.readbyqxmd.com/read/29704008/impact-of-late-onset-alzheimer-s-genetic-risk-factors-on-beta-amyloid-endocytic-production
#5
REVIEW
Cláudia Guimas Almeida, Farzaneh Sadat Mirfakhar, Catarina Perdigão, Tatiana Burrinha
The increased production of the 42 aminoacids long beta-amyloid (Aβ42) peptide has been established as a causal mechanism of the familial early onset Alzheimer's disease (AD). In contrast, the causal mechanisms of the late-onset AD (LOAD), that affects most AD patients, remain to be established. Indeed, Aβ42 accumulation has been detected more than 30 years before diagnosis. Thus, the mechanisms that control Aβ accumulation in LOAD likely go awry long before pathogenesis becomes detectable. Early on, APOE4 was identified as the biggest genetic risk factor for LOAD...
April 27, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29702546/mutation-of-cd2ap-and-sh3kbp1-binding-motif-in-alphavirus-nsp3-hypervariable-domain-results-in-attenuated-virus
#6
Margit Mutso, Ainhoa Moliner Morro, Cecilia Smedberg, Sergo Kasvandik, Muriel Aquilimeba, Mona Teppor, Liisi Tarve, Aleksei Lulla, Valeria Lulla, Sirle Saul, Bastian Thaa, Gerald M McInerney, Andres Merits, Margus Varjak
Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established...
April 27, 2018: Viruses
https://www.readbyqxmd.com/read/29698690/alzheimer-s-disease-susceptibility-genes-modify-the-risk-of-parkinson-disease-and-parkinson-s-disease-associated-cognitive-impairment
#7
Lu Fang, Bei-Sha Tang, Kuan Fan, Chang-Min Wan, Xin-Xiang Yan, Ji-Feng Guo
The pathogenic mechanism underlying Parkinson's disease (PD) and PD- Cognitive impairment (CI) remains elusive. Its potential link to the risk factors in Alzheimer's disease (AD) is unclear. In this study, we analyzed 16 CE-associated single nucleotide polymorphisms (SNPs) in twelve genes in a Chinese cohort of 450 PD cases and 449 controls. Among our 298 cases clinically evaluated for CI, 113 cases did not show CI signs (PD-NC), 86 cases had mildly cognitive impairment (PD-MCI) and 99 cases had dementia (PD-D)...
April 24, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29677049/urinary-podocyte-associated-molecules-and-albuminuria-in-hypertension
#8
Javier Perez-Hernandez, Maria D Olivares, Elena Solaz, Fernando Martinez, Sergio Martínez-Hervas, Gernot Pichler, Felipe J Chaves, Josep Redon, Raquel Cortes
OBJECTIVE: Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and nondiabetic participants. PATIENTS AND METHODS: Sixty-four hypertensive patients, 30 diabetics, with glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m were included. Urinary albumin excretion was measured in morning urine using a nephelometric immunoassay and expressed as albumin/creatinine ratio. Urinary pellets were obtained from fresh urine and mRNA was assessed by real-time quantitative PCR...
April 19, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29520916/identification-and-characterisation-of-a-theileria-annulata-proline-rich-microtubule-and-sh3-domain-interacting-protein-tamiship-that-forms-a-complex-with-clasp1-eb1-and-cd2ap-at-the-schizont-surface
#9
Sandra Huber, Tulin Karagenc, Dominic Ritler, Sven Rottenberg, Kerry Woods
Theileria annulata is an apicomplexan parasite that modifies the phenotype of its host cell completely, inducing uncontrolled proliferation, resistance to apoptosis, and increased invasiveness. The infected cell thus resembles a cancer cell, and changes to various host cell signalling pathways accompany transformation. Most of the molecular mechanisms leading to Theileria-induced immortalization of leukocytes remain unknown. The parasite dissolves the surrounding host cell membrane soon after invasion and starts interacting with host proteins, ensuring its propagation by stably associating with the host cell microtubule network...
March 8, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29397389/recent-studies-on-cellular-and-molecular-mechanisms-in-alzheimer-s-disease-focus-on-epigenetic-factors-and-histone-deacetylase
#10
Harikesh Dubey, Kavita Gulati, Arunabha Ray
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders mainly affecting elderly people. It is characterized by progressive loss of memory and cognitive function. More than 95% of AD cases are related to sporadic or late-onset AD (LOAD). The etiology of LOAD is still unclear. It has been reported that environmental factors and epigenetic alterations play a significant role in AD pathogenesis. Furthermore, recently, genome-wide association studies (GWAS) identified 10 novel risk genes: ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, MS4A6A, MS4A4E, and PICALM, which play an important role for LOAD...
March 28, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29335087/-research-advances-in-the-association-between-transient-receptor-potential-cation-channel-6-and-kidney-disease
#11
REVIEW
Shan Cao, Yun-Guang Liu
Transient receptor potential cation channel 6 (TRPC6) is a member of the transient receptor superfamily encoded by the TRPC6 gene and is widely expressed in tissues and organs of the human body, especially in the glomerular podocytes. TRPC6 interacts with various slit diaphragm (SD) proteins including podocin, nephrin, ACTN4, and CD2AP to maintain the normal structure and function of glomerular podocytes. Foot process fusion caused by podocyte damage due to various factors is the most important morphological change in kidney disease...
January 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29244787/loss-of-podocalyxin-causes-a-novel-syndromic-type-of-congenital-nephrotic-syndrome
#12
Hee Gyung Kang, Moses Lee, Kyoung Boon Lee, Michael Hughes, Bo Sang Kwon, Sangmoon Lee, Kelly M McNagny, Yo Han Ahn, Jung Min Ko, Il-Soo Ha, Murim Choi, Hae Il Cheong
Many cellular structures directly imply specific biological functions. For example, normal slit diaphragm structures that extend from podocyte foot processes ensure the filtering function of renal glomeruli. These slits are covered by a number of surface proteins, such as nephrin, podocin, podocalyxin and CD2AP. Here we report a human patient presenting with congenital nephrotic syndrome, omphalocele and microcoria due to two loss-of-function mutations in PODXL, which encodes podocalyxin, inherited from each parent...
December 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29175910/paws1-controls-cytoskeletal-dynamics-and-cell-migration-through-association-with-the-sh3-adaptor-cd2ap
#13
Timothy D Cummins, Kevin Z L Wu, Polyxeni Bozatzi, Kevin S Dingwell, Thomas J Macartney, Nicola T Wood, Joby Varghese, Robert Gourlay, David G Campbell, Alan Prescott, Eric Griffis, James C Smith, Gopal P Sapkota
Our previous studies of PAWS1 (protein associated with SMAD1; also known as FAM83G) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1-knockout U2OS osteosarcoma cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization...
January 10, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29133184/jnk-is-antagonized-to-ensure-the-correct-number-of-interommatidial-cells-pattern-the-drosophila-retina
#14
Henry L Bushnell, Christina E Feiler, Kwami F Ketosugbo, Mark B Hellerman, Valerie L Nazzaro, Ruth I Johnson
Apoptosis is crucial during the morphogenesis of most organs and tissues, and is utilized for tissues to achieve their proper size, shape and patterning. Many signaling pathways contribute to the precise regulation of apoptosis. Here we show that Jun N-terminal Kinase (JNK) activity contributes to the coordinated removal of interommatidial cells via apoptosis in the Drosophila pupal retina. This is consistent with previous findings that JNK activity promotes apoptosis in other epithelia. However, we found that JNK activity is repressed by Cindr (the CIN85 and CD2AP ortholog) in order to promote cell survival...
January 1, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29038887/mutations-in-inf2-may-be-associated-with-renal-histology-other-than-focal-segmental-glomerulosclerosis
#15
Anja K Büscher, Nora Celebi, Peter F Hoyer, Hanns-Georg Klein, Stefanie Weber, Julia Hoefele
BACKGROUND: In 2010, INF2 mutations were associated with autosomal-dominant focal segmental glomerulosclerosis (FSGS), clinically presenting with moderate proteinuria in adolescence. However, in the meantime, cases with more severe clinical courses have been described, including progression to end-stage renal disease (ESRD) during childhood. INF2 mutations in patients with isolated FSGS are clustered in exons 2 to 4, encoding the diaphanous inhibitory domain, involved in the regulation of the podocyte actin cytoskeleton...
March 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28986432/adaptor-protein-cd2ap-and-l-type-lectin-lman2-regulate-exosome-cargo-protein-trafficking-through-the-golgi-complex
#16
Sang-Ho Kwon, Sekyung Oh, Marisa Nacke, Keith E Mostov, Joshua H Lipschutz
No abstract text is available yet for this article.
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28984604/alzheimer-s-disease-related-polymorphisms-in-shunt-responsive-idiopathic-normal-pressure-hydrocephalus
#17
Joel Huovinen, Seppo Helisalmi, Jussi Paananen, Tiina Laiterä, Maria Kojoukhova, Anna Sutela, Ritva Vanninen, Marjo Laitinen, Tuomas Rauramaa, Anne M Koivisto, Anne M Remes, Hilkka Soininen, Mitja Kurki, Annakaisa Haapasalo, Juha E Jääskeläinen, Mikko Hiltunen, Ville Leinonen
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a late onset, surgically treated progressive brain disease caused by impaired cerebrospinal fluid dynamics and subsequent ventriculomegaly. Comorbid Alzheimer's disease (AD) seems to be frequent in iNPH. OBJECTIVE: We aim to evaluate the role of AD-related polymorphisms in iNPH. METHODS: Overall 188 shunt-operated iNPH patients and 688 controls without diagnosed neurodegenerative disease were included into analysis...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28878342/inhibition-of-ship2-in-cd2ap-deficient-podocytes-ameliorates-reactive-oxygen-species-generation-but-aggravates-apoptosis
#18
Pauliina Saurus, Tuomas A Tolvanen, Sonja Lindfors, Sara Kuusela, Harry Holthöfer, Eero Lehtonen, Sanna Lehtonen
Lack of CD2-associated protein (CD2AP) in mice increases podocyte apoptosis and leads to glomerulosclerosis and renal failure. We showed previously that SHIP2, a negative regulator of the PI3K/AKT signalling pathway, interacts with CD2AP. Here, we found that the expression level and activity of SHIP2 and production of reactive oxygen species (ROS) are increased in cultured CD2AP knockout (CD2AP-/-) mouse podocytes. Oxidative stress was also increased in CD2AP-/- mouse glomeruli in vivo. We found that puromycin aminonucleoside (PA), known to increase ROS production and apoptosis, increases SHIP2 activity and reduces CD2AP expression in cultured human podocytes...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814739/re-characterization-of-the-glomerulopathy-in-cd2ap-deficient-mice-by-high-resolution-helium-ion-scanning-microscopy
#19
Kenji Tsuji, Teodor G Păunescu, Hani Suleiman, Dongping Xie, Fahmy A Mamuya, Jeffrey H Miner, Hua A Jenny Lu
Helium ion scanning microscopy (HIM) is a novel technology that directly visualizes the cell surface ultrastructure without surface coating. Despite its very high resolution, it has not been applied extensively to study biological or pathology samples. Here we report the application of this powerful technology to examine the three-dimensional ultrastructural characteristics of proteinuric glomerulopathy in mice with CD2-associated protein (CD2AP) deficiency. HIM revealed the serial alteration of glomerular features including effacement and disorganization of the slit diaphragm, followed by foot process disappearance, flattening and fusion of major processes, and eventual transformation into a podocyte sheet as the disease progressed...
August 16, 2017: Scientific Reports
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
#20
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...
2017: Cellular Physiology and Biochemistry
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