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https://www.readbyqxmd.com/read/28919327/endothelial-microparticle-promoted-inhibition-of-vascular-remodeling-is-abrogated-under-hyperglycaemic-conditions
#1
Felix Jansen, Andreas Zietzer, Tobias Stumpf, Anna Flender, Theresa Schmitz, Georg Nickenig, Nikos Werner
BACKGROUND: Endothelial microparticles (EMPs) inhibit vascular remodeling by transferring functional microRNA (miRNA) into target vascular smooth muscle cells (VSMCs). Because EMPs are increased in diabetic patients and potentially linked to vascular complications in diabetes mellitus, we sought to determine whether effects of EMPs generated under high glucose concentration on vascular remodeling might differ from EMPs derived from untreated cells. METHODS AND RESULTS: EMPs were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions...
September 14, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28880263/lrp6-is-identified-as-a-potential-prognostic-marker-for-oral-squamous-cell-carcinoma-via-maldi-ims
#2
Yao Yuan, Xiaoyan Xie, Yuchen Jiang, Zihao Wei, Peiqi Wang, Fangman Chen, Xinyi Li, Chongkui Sun, Hang Zhao, Xin Zeng, Lu Jiang, Yu Zhou, Hongxia Dan, Mingye Feng, Rui Liu, Zhiyong Wang, Qianming Chen
Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, with 500 000 new cases each year. However, the mechanisms underlying OSCC development are relatively unknown. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was used to profile the differentially expressed peptides/proteins between OSCC tissues and their adjacent noncancerous tissues. Sixty-seven unique peptide peaks and five distinct proteins were identified with changed expression levels...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28870205/maintenance-of-stemness-is-associated-with-the-interation-of-lrp6-and-heparin-binding-protein-ccn2-autocrined-by-hepatocellular-carcinoma
#3
Qingan Jia, Yang Bu, Zhiming Wang, Bendong Chen, Qiangbo Zhang, Songning Yu, Qingguang Liu
BACKGROUND: The overall response rate of hepatocellular carcinoma (HCC) to chemotherapy is poor. In our previous study, oxaliplatin-resistant HCC is found to exhibit an enhanced stemness, and increased levels of CCN2 and LRP6, while the role of CCN2 and LRP6 in the prognosis of HCC patients, and the interaction regulation mechanism between CCN2 and LRP6 are still unclear. METHODS: The expression levels of CCN2 and LRP6 were detected in large cohorts of HCCs, and functional analyses of CCN2 and LRP6 were performed both in vitro and in vivo...
September 4, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28861168/inhibition-of-wnt-%C3%AE-catenin-by-anthelmintic-drug-niclosamide-effectively-targets-growth-survival-and-angiogenesis-of-retinoblastoma
#4
Zhi Li, Qin Li, Genguo Wang, Yi Huang, Xiaochun Mao, Yanfang Zhang, Xueyan Wang
Retinoblastoma is an angiogenesis-dependent ocular tumor, the clinical management of which remains a challenge. Agents that can target tumor cells and angiogenesis, as well as augment current chemotherapy efficacy, present a promising therapeutic strategy for retinoblastoma. We demonstrated that niclosamide, an FDA-approved anthelmintic drug, is effective against multiple aspects of retinoblastoma. Niclosamide inhibited proliferation via causing cell cycle arrest at the G2/M phase and induced caspase-dependent apoptosis in a panel of retinoblastoma cell lines, including Y79, RB116, and WERI-Rb-1...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#5
Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto, Akira Kikuchi
Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane-a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL...
August 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28815294/diallyl-trisulfide-inhibits-proliferation-invasion-and-angiogenesis-of-glioma-cells-by-inactivating-wnt-%C3%AE-catenin-signaling
#6
Qingxia Tao, Cuiying Wu, Ruxiang Xu, Lijun Niu, Jiazhen Qin, Ning Liu, Peng Zhang, Chong Wang
Aberrant activation of Wnt/β-catenin signaling leads to increased cell proliferation and survival and promotes the development of various human tumors, including glioma, one of the most common primary brain tumors. The treatment efficacy of many anticancer drugs remains limited or unsatisfactory and it is urgently necessary to develop effective and low-toxicity anticancer drugs or strategies, especially for glioma. Here, we report that diallyl trisulfide suppresses survival, migration, invasion and angiogenesis in glioma cells...
August 17, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28813618/whole-exome-sequencing-identifies-novel-variants-for-tooth-agenesis
#7
N Dinckan, R Du, L E Petty, Z Coban-Akdemir, S N Jhangiani, I Paine, E H Baugh, A P Erdem, H Kayserili, H Doddapaneni, J Hu, D M Muzny, E Boerwinkle, R A Gibbs, J R Lupski, Z O Uyguner, J E Below, A Letra
Tooth agenesis is a common craniofacial abnormality in humans and represents failure to develop 1 or more permanent teeth. Tooth agenesis is complex, and variations in about a dozen genes have been reported as contributing to the etiology. Here, we combined whole-exome sequencing, array-based genotyping, and linkage analysis to identify putative pathogenic variants in candidate disease genes for tooth agenesis in 10 multiplex Turkish families. Novel homozygous and heterozygous variants in LRP6, DKK1, LAMA3, and COL17A1 genes, as well as known variants in WNT10A, were identified as likely pathogenic in isolated tooth agenesis...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28752891/inhibition-of-nuclear-wnt-signaling-challenges-of-an-elusive-target-for-cancer-therapy
#8
REVIEW
Yung Lyou, Amber N Habowski, George T Chen, Marian L Waterman
The highly conserved Wnt signaling pathway plays an important role in embryonic development and disease pathogenesis, most notably cancer. The "canonical," or β-catenin-dependent Wnt signal initiates at the cell plasma membrane with the binding of Wnt proteins to Frizzled:LRP5/LRP6 receptor complexes, and is mediated by the translocation of the transcription co-activator protein, β-catenin, into the nucleus. β-catenin then forms a complex with TCF/LEF transcription factors to regulate multiple gene programs...
July 28, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28741966/the-connections-of-wnt-pathway-components-with-cell-cycle-and-centrosome-side-effects-or-a-hidden-logic
#9
Vítězslav Bryja, Igor Červenka, Lukáš Čajánek
Wnt signaling cascade has developed together with multicellularity to orchestrate the development and homeostasis of complex structures. Wnt pathway components - such as β-catenin, Dishevelled (DVL), Lrp6, and Axin-- are often dedicated proteins that emerged in evolution together with the Wnt signaling cascade and are believed to function primarily in the Wnt cascade. It is interesting to see that in recent literature many of these proteins are connected with cellular functions that are more ancient and not limited to multicellular organisms - such as cell cycle regulation, centrosome biology, or cell division...
July 25, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#10
Austin Gay, Dwight A Towler
PURPOSE OF REVIEW: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis. RECENT FINDINGS: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease...
October 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28697798/a-proteomic-analysis-of-lrrk2-binding-partners-reveals-interactions-with-multiple-signaling-components-of-the-wnt-pcp-pathway
#11
Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja, Ernest Arenas
BACKGROUND: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients...
July 11, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28696417/harnessing-low-density-lipoprotein-receptor-protein-6-lrp6-genetic-variation-and-wnt-signaling-for-innovative-diagnostics-in-complex-diseases
#12
REVIEW
Z-M Wang, J-Q Luo, L-Y Xu, H-H Zhou, W Zhang
Wnt signaling regulates a broad variety of processes in both embryonic development and various diseases. Recent studies indicated that some genetic variants in Wnt signaling pathway may serve as predictors of diseases. Low-density lipoprotein receptor protein 6 (LRP6) is a Wnt co-receptor with essential functions in the Wnt/β-catenin pathway, and mutations in LRP6 gene are linked to many complex human diseases, including metabolic syndrome, cancer, Alzheimer's disease and osteoporosis. Therefore, we focus on the role of LRP6 genetic polymorphisms and Wnt signaling in complex diseases, and the mechanisms from mouse models and cell lines...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28694256/multiple-modes-of-lrp4-function-in-modulation-of-wnt-%C3%AE-catenin-signaling-during-tooth-development
#13
Youngwook Ahn, Carrie Sims, Megan J Murray, Paige K Kuhlmann, Jesús Fuentes-Antrás, Scott D Weatherbee, Robb Krumlauf
During development and homeostasis, precise control of Wnt/β-catenin signaling is in part achieved by secreted and membrane proteins that negatively control activity of the Wnt co-receptors Lrp5 and Lrp6. Lrp4 is related to Lrp5/6 and is implicated in modulation of Wnt/β-catenin signaling, presumably through its ability to bind to the Wise (Sostdc1)/sclerostin (Sost) family of Wnt antagonists. To gain insights into the molecular mechanisms of Lrp4 function in modulating Wnt signaling, we performed an array of genetic analyses in murine tooth development, where Lrp4 and Wise play important roles...
August 1, 2017: Development
https://www.readbyqxmd.com/read/28679315/bone-marrow-mesenchymal-stem-cell-derived-cd63-exosomes-transport-wnt3a-exteriorly-and-enhance-dermal-fibroblast-proliferation-migration-and-angiogenesis-in-vitro
#14
Jeffrey D McBride, Luis Menocal-Rodriguez, Ambar Candanedo, Wellington Guzman, Marta Garcia-Contreras, Evangelos Van Badiavas
Wnts are secreted glycoproteins that regulate stem cell self-renewal, differentiation, and cell-to-cell communication during embryonic development and in adult tissues. Bone marrow mesenchymal stem cells (BM-MSCs) have been shown to stimulate dermis repair and regeneration; however, it is unclear how BM-MSCs may modulate downstream Wnt signaling. While recent reports implicate that Wnt ligands and Wnt messenger RNAs (such as Wnt4) exist within the interior compartment of exosomes, it has been debated whether or not Wnts exist on the exterior surface of exosomes to travel in the extracellular space...
July 5, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28674183/n-terminal-part-of-dishevelled-dep-domain-is-required-for-wnt-%C3%AE-catenin-signaling-in-mammalian-cells
#15
Petra Paclíková, Ondřej Bernatík, Tomasz Witold Radaszkiewicz, Vítězslav Bryja
Dishevelled (DVL) proteins are key mediators of Wnt/β-catenin signaling pathway. All DVL proteins contain three conserved domains -- DIX, PDZ and DEP. There is a consensus in the field that DIX domain is critical for Wnt/β-catenin signaling but contradictory evidence exists regarding the function of the DEP domain. It has been difficult until recently to test the importance of the DEP domain rigorously because of the interference with endogenous DVL, expressed in all Wnt-responsive cell lines. In this study, we took advantage of DVL KO (DVL1/DVL2/DVL3-triple knockout) cells, fully deficient in Wnt3a-induced signaling events, and performed series of rescue experiments...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28586911/serpina3k-ameliorates-the-corneal-oxidative-injury-induced-by-4-hydroxynonenal
#16
Xiling Zheng, Huixia Cui, Yuanyuan Yin, Yajing Zhang, Rongrong Zong, Xiaorui Bao, Jian-Xing Ma, Zuguo Liu, Yueping Zhou
Purpose: We previously demonstrated that SERPINA3K has anti-inflammatory, antiangiogenic, and antioxidant effects in corneas. Here we further investigated the effects of SERPINA3K on the corneal oxidant injury setting recently developed and induced by 4-hydroxynonenal (4-HNE). Methods: We applied the 4-HNE-induced corneal oxidant stress in cultured human corneal epithelial (HCE) cells in vitro and to the cornea of rats in vivo. The following experiments were conducted: cell counting kit 8 assay to detect cell viability; quantitative real-time PCR assay; Western blotting and immunofluorescent staining to measure gene expressions or protein levels of key reactive oxygen species (ROS)-associated factors (3-nitrotyrosine [3-NT]; nicotinamide adenine dinucleotide phosphate [NADPH]-oxidase 4 [NOX4]; superoxide dismutase [SOD]); catalase and nuclear factor [erythroid-derived 2]-like 2 [NRF2]); as well as main factors of the Wnt/β-catenin signaling pathway (p-LRP6, β-catenin and transcription factor 4 [TCF4]); histologic staining; and TUNEL staining to examine sections of rat corneas...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28569772/deficiency-of-pigment-epithelium-derived-factor-in-nasopharyngeal-carcinoma-cells-triggers-the-epithelial-mesenchymal-transition-and-metastasis
#17
Ting Zhang, Ping Yin, Zichen Zhang, Banglao Xu, Di Che, Zhiyu Dai, Chang Dong, Ping Jiang, Honghai Hong, Zhonghan Yang, Ti Zhou, Jianyong Shao, Zumin Xu, Xia Yang, Guoquan Gao
Distant metastasis is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure while epithelial-mesenchymal transition (EMT) is the critical process of NPC invasion and metastasis. However, tumor-suppressor genes involved in the EMT and metastasis of NPC have not been explored clearly compared with the oncogenes. In the present study, the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antitumor factor, was diminished in human NPC tissues and associated with clinicopathological and EMT features...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28549041/value-of-osteoblast-derived-exosomes-in-bone-diseases
#18
Min Ge, Yingzhi Wu, Ronghu Ke, Tianyi Cai, Junyi Yang, Xiongzheng Mu
PURPOSE: The authors' purpose is to reveal the value of osteoblast-derived exosomes in bone diseases. METHODS: Microvesicles from supernatants of mouse Mc3t3 were isolated by ultracentrifugation and then the authors presented the protein profile by proteomics analysis. RESULTS: The authors detected a total number of 1536 proteins by mass spectrometry and found 172 proteins overlap with bone database. The Ingenuity Pathway Analysis shows network of "Skeletal and Muscular System Development and Function, Developmental Disorder, Hereditary Disorder" and pathway about osteogenesis...
June 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#19
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28521288/hypermethylation-of-ndn-promotes-cell-proliferation-by-activating-the-wnt-signaling-pathway-in-colorectal-cancer
#20
Yu-Han Hu, Qing Chen, Yan-Xia Lu, Jian-Ming Zhang, Chun Lin, Fan Zhang, Wen-Juan Zhang, Xiao-Min Li, Wei Zhang, Xue-Nong Li
The progression of CRC is a multistep process involving several genetic changes or epigenetic modifications. NDN is a member of the MAGE family, encoding a protein that generally suppresses cell proliferation and acting as a transcriptional repressor. Immunohistochemical staining revealed that the expression of NDN was significantly down-regulated in CRC tissues compared with normal tissues and the down-regulation of NDN in CRC could reflect the hypermethylation of the NDN promoter. Treatment of the CRC cell line SW480 with the demethylating agent 5-Aza-CdR restored the NDN expression level...
July 11, 2017: Oncotarget
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