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https://www.readbyqxmd.com/read/28072409/alcohol-dose-dependent-dna-methylation-and-expression-in-the-nucleus-accumbens-identifies-coordinated-regulation-of-synaptic-genes
#1
R Cervera-Juanes, L J Wilhelm, B Park, K A Grant, B Ferguson
Alterations in DNA methylation have been associated with alcohol exposure and proposed to contribute to continued alcohol use; however, the molecular mechanisms involved remain obscure. We investigated the escalating effects of alcohol use on DNA methylation, gene expression and predicted neural effects in the nucleus accumbens of rhesus macaques that self-administered 4% alcohol for over 12 months. Using an exploratory approach to identify CpG-rich regions, followed by bisulfite sequencing, the methylation levels of 2...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28067456/type-2-diabetes-mellitus-associated-with-the-interaction-of-lrp5-polymorphism-and-overweight-and-obesity-in-rural-chinese-adults
#2
Zhang Lu, Wang Jinjin, Zhang Ming, Wang Guo'an, Shen Yanxia, Wu Dongting, Wang Chongjian, Li Linlin, Ren Yongcheng, Wang Bingyuan, Zhang Hongyan, Yang Xiangyu, Zhao Yang, Han Chengyi, Zhou Junmei, Pang Chao, Yin Lei, Zhao Jingzhi, Luo Xinping, Hu Dongsheng
BACKGROUND: Low-density lipoprotein receptor-related protein 5 (LRP5) plays an important role in glucose and cholesterol metabolism, so a cohort study was used to evaluate the association of LRP5 variants and incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. METHODS: A total of 7751 subjects ≥18 years old and without T2DM underwent genotyping at baseline; 6326 subjects (81.62%) were followed-up, with 5511 eligible for this analysis...
January 9, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28063934/morphine-administration-induces-change-in-anxiety-related-behavior-via-wnt-%C3%AE-catenin-signaling
#3
Jiancai Wang, Gang Zhu, Lu Huang, Tiejian Nie, Kai Tao, Yuqian Li, Guodong Gao
Chronic morphine administration is known to decrease anxiety-related behavior, which may lead to morphine-seeking and other social problems. Recent studies have revealed that Wnt/β-catenin signaling plays an important role in anxiety-related behavior. We used HT22 cells, which were derived from primary mouse hippocampal neuronal cultures, to explore the relationship between Wnt signaling and morphine exposure. Many techniques, such as western blot analysis, immunofluorescence and luciferase assays, were utilized...
January 4, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#4
Robert Böscke, Eszter K Vladar, Michael Könnecke, Birgit Hüsing, Robert Linke, Ralph Pries, Norbert Reiling, Jeffrey D Axelrod, Jayakar V Nayak, Barbara Wollenberg
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28056548/l-carnitine-contributes-to-enhancement-of-neurogenesis-from-mesenchymal-stem-cells-through-wnt-%C3%AE-catenin-and-pka-pathway
#5
Ezzatollah Fathi, Raheleh Farahzadi, Hojjatollah N Charoudeh
The identification of factors capable of enhancing neurogenesis has great potential for cellular therapies in neurodegenerative diseases. Multiple studies have shown the neuroprotective effects of L-carnitine (LC). This study determined whether neuronal differentiation of rat adipose tissue-derived mesenchymal stem cells (ADSCs) can be activated by LC. In this study, protein kinase A (PKA) and Wnt/β-catenin pathways were detected to show if this activation was due to these pathways. The expression of LC-induced neurogenesis markers in ADSCs was characterized using real-time PCR...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28049091/taspine-derivative-12k-suppressed-a549-cell-migration-through-the-wnt-%C3%AE-catenin-and-ephrinb2-signaling-pathway
#6
Bingling Dai, Yujiao Ma, Tianfeng Yang, Wenjie Wang, Yanmin Zhang
12k, a taspine derivative, has been demonstrated to have the potent anti-tumor activity in lung cancer and colorectal cancer. The study aims to further explore the underlying mechanisms of 12k on A549 cell migration in vitro. Our data demonstrated that 12k negatively regulated Wnt signaling pathway by suppressing the phosphorylation of LRP5/6, and inhibiting the expression and nuclear translocation of β-catenin. 12k was shown to downregulate MMP3 and MMP7 expression which regulated by β-catenin interacts with TCF/LEF in the nucleus, and effectively impaired the related migration protein expression of MMP2 and MMP9 in A549 cells...
December 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28028632/the-rs3736228-polymorphism-in-the-lrp5-gene-is-associated-with-calcaneal-ultrasound-parameter-but-not-with-body-composition-in-a-cohort-of-young-caucasian-adults
#7
María Correa-Rodríguez, Jacqueline Schmidt-RioValle, Blanca Rueda-Medina
The aim of the present study was to investigate the possible influence of low-density lipoprotein receptor-related protein 5 (LRP5) and sclerostin (SOST) genes as genetic factors contributing to calcaneal quantitative ultrasound (QUS) and body composition variables in a population of young Caucasian adults. The study population comprised a total of 575 individuals (mean age 20.41years; SD 2.36) whose bone mass was assessed through QUS to determine broadband ultrasound attenuation (BUA, dB/MHz). Body composition measurements were performed using a body composition analyser...
December 27, 2016: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28002565/large-deletions-of-tspan12-cause-familial-exudative-vitreoretinopathy-fevr
#8
Soo Hyun Seo, Man Jin Kim, Sung Wook Park, Jeong Hun Kim, Young Suk Yu, Ji Yun Song, Sung Im Cho, Joo Hyun Ahn, Yeon Hee Oh, Jee-Soo Lee, Seungjun Lee, Moon-Woo Seong, Sung Sup Park, Ji Yeon Kim
Purpose: Familial exudative vitreoretinopathy (FEVR) is a rare, hereditary visual disorder. The gene TSPAN12 is associated with autosomal dominant inheritance of FEVR. The prevalence and impact of large deletions/duplications of TSPAN12 on FEVR patients is unknown. To glean better insight of TSPAN12 on FEVR pathology, herein, we describe three FEVR patients with TSPAN12 deletions. Methods: Thirty-three Korean FEVR patients, who previously screened negative for TSPAN12 mutations, mutations in other FEVR-associated genes such as NDP, FZD4, LRP5, and large deletions and duplications of NDP, FZD4, and LRP5, were selected for TSPAN12 large deletion and duplication analyses...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27922964/the-effect-of-uniaxial-mechanical-stretch-on-wnt-%C3%AE-catenin-pathway-in-bone-mesenchymal-stem-cells
#9
Chuang Zhao, Yunfeng Li, Xuemei Wang, Shujuan Zou, Jing Hu, En Luo
Wnt/β-catenin signal is required in bone formation and remodling, but little is known about whether Wnt/β-catenin signal could promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) after uniaxial mechanical stretch. In this study, rat BMSCs were identified by flow cytometry and used for mechanical stretch. A custom-made uniaxial dynamic stretch apparatus was applied for rat BMSCs stretch. There were 2 groups in the study: the mechanical stretch group and the nonstretch control group...
December 5, 2016: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/27833587/a-candidate-gene-association-study-of-bone-mineral-density-in-an-iranian-population
#10
Seyed Alireza Dastgheib, Alison Gartland, Seyed Mohammad Bagher Tabei, Gholamhossein Ranjbar Omrani, Marion Dawn Teare
The genetic epidemiology of variation in bone mineral density (BMD) and osteoporosis is not well studied in Iranian populations and needs more research. We report a candidate gene association study of BMD variation in a healthy cross-sectional study of 501 males and females sampled from the Iranian Multi-Centre Osteoporosis Study, Shiraz, Iran. We selected to study the association with 21 single nucleotide polymorphisms (SNPs) located in the 7 candidate genes LRP5, RANK, RANKL, OPG, P2RX7, VDR, and ESR1. BMD was measured at the three sites L2-L4, neck of femur, and total hip...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27821587/activation-proliferation-associated-protein-2-caprin-2-positively-regulates-cdk14-cyclin-y-mediated-lipoprotein-receptor-related-protein-5-and-6-lrp5-6-constitutive-phosphorylation
#11
Xin Wang, Yingying Jia, Cong Fei, Xiaomin Song, Lin Li
Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are co-receptors for Wnt ligands. Upon ligand binding, LRP5/6 undergo glycogen synthase kinase 3 (GSK3)/casein kinase I (CKI)-mediated phosphorylation at multiple PPP(S/T)P motifs in the intracellular domain, which is essential for canonical Wnt signal transduction. On the other hand, in the Wnt-off state, the mitosis-specific CDK14-Cyclin Y kinase complex phosphorylates Ser-1490 of LRP5/6 at G2/M, thereby priming the receptor for Wnt-induced phosphorylation...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27803037/opposing-roles-of-wnt-inhibitors-igfbp-4-and-dkk1-in-cardiac-ischemia-by-differential-targeting-of-lrp5-6-and-%C3%AE-catenin
#12
Da Wo, Jinhui Peng, Dan-Ni Ren, Liman Qiu, Jinxiao Chen, Ye Zhu, Yingjing Yan, Hongwei Yan, Jian Wu, En Ma, Tao P Zhong, Yihan Chen, Zhongmin Liu, Shangfeng Liu, Luoquan Ao, Zhenping Liu, Cizhong Jiang, Jun Peng, Yunzeng Zou, Qirong Qian, Weidong Zhu
BACKGROUND: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide, triggering irreversible myocardial cell damage and heart failure. The role of low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) as coreceptors of the Wnt/β-catenin pathway in the adult heart remain unknown. Insulin-like growth factor binding protein 4 and dickkopf-related protein 1 (Dkk1) are 2 secreted LRP5/6 binding proteins that play a crucial role in heart development through preventing Wnt/β-catenin pathway activation...
December 13, 2016: Circulation
https://www.readbyqxmd.com/read/27780792/application-of-anti-sclerostin-therapy-in-non-osteoporosis-disease-models
#13
Christina M Jacobsen
Sclerostin, a known inhibitor of the low density lipoprotein related protein 5 and 6 (LRP5 and LRP6) cell surface signaling receptors, is integral in the maintenance of normal bone mass and strength. Patients with loss of function mutations in SOST or missense mutations in LRP5 that prevent Sclerostin from binding and inhibiting the receptor, have significantly increased bone mass. This observation leads to the development of Sclerostin neutralizing therapies to increase bone mass and strength. Anti-Sclerostin therapy has been shown to be effective at increasing bone density and strength in animal models and patients with osteoporosis...
October 22, 2016: Bone
https://www.readbyqxmd.com/read/27751348/lrp5-signaling-in-osteosarcomagenesis-a-cautionary-tale-of-translation-from-cell-lines-to-tumors
#14
Logan Horne, Frank R Avilucea, Huifeng Jin, Jared J Barrott, Kyllie Smith-Fry, Yanliang Wang, Bang H Hoang, Kevin B Jones
Previous reports document expression of low-density lipoprotein receptor-related protein 5 (LRP5) in osteosarcoma (OS) tissue. Expression of this Wnt receptor correlated with metastatic disease and poor disease-free survival. Forced expression of dominant-negative LRP5 (dnLRP5), which lacks the membrane binding domain of the native protein and therefore functions as a soluble receptor-sponge for Wnt ligands, reduced in vitro cellular invasion and in vivo xenograft tumor growth for osteosarcoma cell lines. Here, we use a genetically engineered mouse model of osteosarcomagenesis with and without expression of dnLRP5 to assess to what degree tumorigenesis is affected and whether Wnt/β-catenin signaling is circumvented or maintained...
October 2016: Translational Oncology
https://www.readbyqxmd.com/read/27720905/a-dynamic-wnt-%C3%AE-catenin-signaling-environment-leads-to-wnt-independent-and-wnt-dependent-proliferation-of-embryonic-intestinal-progenitor-cells
#15
Alana M Chin, Yu-Hwai Tsai, Stacy R Finkbeiner, Melinda S Nagy, Emily M Walker, Nicole J Ethen, Bart O Williams, Michele A Battle, Jason R Spence
Much of our understanding about how intestinal stem and progenitor cells are regulated comes from studying the late fetal stages of development and the adult intestine. In this light, little is known about intestine development prior to the formation of stereotypical villus structures with columnar epithelium, a stage when the epithelium is pseudostratified and appears to be a relatively uniform population of progenitor cells with high proliferative capacity. Here, we investigated a role for WNT/β-CATENIN signaling during the pseudostratified stages of development (E13...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27704249/lrp5-canonical-wnt-signalling-and-healing-of-ischemic-myocardium
#16
M Borrell-Pages, G Vilahur, J C Romero, L Casaní, M T Bejar, L Badimon
LRP5 (low-density lipoprotein receptor-related protein 5) activates canonical Wnt signalling. LRP5 plays multiple roles including regulation of lipoprotein and cholesterol homeostasis as well as innate immunity cell function. However, it is not known whether LRP5 has a role in the myocardium. The aim of this study was to investigate LRP5 and Wnt signalling in myocardial remodelling after acute myocardial infarction (MI). Wnt protein levels were determined in a hypercholesterolemic porcine model of MI, in Lrp5 (-/-) C57Bl6 mice, in cultured cardiomyocytes and in human explanted hearts with previous MI episodes...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27698794/two-novel-susceptibility-loci-for-non-small-cell-lung-cancer-map-to-low-density-lipoprotein-receptor-related-protein-5
#17
Ying Wang, Yongjun Zhang, Meiyu Fang, Wenglong Bao, Dehou Deng
This study investigated the effect of single-nucleotide polymorphisms (SNPs) of low-density lipoprotein receptor-related protein 5 (LRP5) on the risk of developing non-small cell lung cancer (NSCLC). A total of 500 NSCLC patients and 500 healthy controls were recruited for genotyping of 11 SNPs of LRP5. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses. Eleven Tag SNPs were detected...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27680891/macrophages-of-genetically-characterized-familial-hypercholesterolaemia-patients-show-up-regulation-of-ldl-receptor-related-proteins
#18
Rafael Escate, Teresa Padro, Maria Borrell-Pages, Rosa Suades, Rosa Aledo, Pedro Mata, Lina Badimon
Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL...
September 29, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27668462/lrp5-%C3%AE-catenin-signaling-controls-lung-macrophage-differentiation-and-inhibits-resolution-of-fibrosis
#19
Joseph A Sennello, Alexander V Misharin, Annette S Flozak, Sergejs Berdnikovs, Paul Cheresh, John Varga, David W Kamp, G R Scott Budinger, Cara J Gottardi, Anna P Lam
Previous studies established that attenuating Wnt/β-catenin signaling limits lung fibrosis in the bleomycin mouse model of this disease, but the contribution of this pathway to distinct lung cell phenotypes relevant to tissue repair and fibrosis remains incompletely understood. Using microarray analysis, we found that bleomycin-injured lungs from mice that lack the Wnt co-receptor Lrp5 and exhibit reduced fibrosis, showed enrichment for pathways related to extracellular matrix processing, immunity, and lymphocyte proliferation, suggesting the contribution of an immune-matrix remodeling axis relevant to fibrosis...
September 26, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27666889/-effects-of-0-5-gy-x-ray-radiation-on-the-profile-of-gene-expression-in-mc3t3-e1-osteoblasts
#20
M Chen, Q R Dong, Q Huang, W Xu, C She
Objective: To investigate the molecular mechanism of low-dose X-ray irradiation on osteoblasts by detecting the gene expression profiles of osteoblasts radiated with 0.5 Gy X-ray. Methods: Microarray analyses to value the changes of gene expression of MC3T3-E1 osteoblasts after 0.5 Gy X-ray irradiation were conducted.The end points included modulation of key markers, and pathway and gene ontology through transcriptomic profiling and bioinformatics analysis. Several major genes during osteoblasts differentiation were selected for Real-time PCR analysis...
September 6, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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