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https://www.readbyqxmd.com/read/28918952/a-dual-function-for-prickle-in-regulating-frizzled-stability-during-feedback-dependent-amplification-of-planar-polarity
#1
Samantha J Warrington, Helen Strutt, Katherine H Fisher, David Strutt
The core planar polarity pathway coordinates epithelial cell polarity during animal development, and loss of its activity gives rise to a range of defects, from aberrant morphogenetic cell movements to failure to correctly orient structures, such as hairs and cilia. The core pathway functions via a mechanism involving segregation of its protein components to opposite cells ends, where they form asymmetric intracellular complexes that couple cell-cell polarity. This segregation is a self-organizing process driven by feedback interactions between the core proteins themselves...
September 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28916299/non-canonical-wnt-mediated-neurogenic-differentiation-of-human-bone-marrow-derived-mesenchymal-stem-cells
#2
Sujeong Jang, Hyong-Ho Cho, Jong-Seong Park, Han-Seong Jeong
Bone marrow-derived mesenchymal stem cells (BM-MSCs), which are characterized by multipotency and self-renewal, are responsible for tissue regeneration and repair. We have previously reported in adipose tissue-derived MSCs that only Wnt5a is enhanced at neurogenic differentiation, and the mechanism of differentiation is dependent on the Wnt5a/JNK pathway; however, the role of Wnt/MAPK pathway is yet to be investigated in neurogenic differentiation in BM-MSCs. We compared the transcriptional expression of Wnt in neurogenic induced-hBM-MSCs (NI-hBM-MSCs) with that in primary hBM-MSCs, using RT-PCR, qPCR, and western blotting...
September 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28874201/tetrahydrobiopterin-bh4-deficiency-is-associated-with-augmented-inflammation-and-microvascular-degeneration-in-the-retina
#3
José Carlos Rivera, Baraa Noueihed, Ankush Madaan, Isabelle Lahaie, Jingyi Pan, Jaques Belik, Sylvain Chemtob
BACKGROUND: Tetrahydrobiopterin (BH4) is an essential cofactor in multiple metabolic processes and plays an essential role in maintaining the inflammatory and neurovascular homeostasis. In this study, we have investigated the deleterious effects of BH4 deficiency on retinal vasculature during development. METHODS: hph-1 mice, which display deficiency in BH4 synthesis, were used to characterize the inflammatory effects and the integrity of retinal microvasculature...
September 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28855860/transcriptional-reorganization-of-drosophila-motor-neurons-and-their-muscular-junctions-toward-a-neuroendocrine-phenotype-by-the-bhlh-protein-dimmed
#4
Jiangnan Luo, Yiting Liu, Dick R Nässel
Neuroendocrine cells store and secrete bulk amounts of neuropeptides, and display morphological and molecular characteristics distinct from neurons signaling with classical neurotransmitters. In Drosophila the transcription factor Dimmed (Dimm), is a prime organizer of neuroendocrine capacity in a majority of the peptidergic neurons. These neurons display large cell bodies and extensive axon terminations that commonly do not form regular synapses. We ask which molecular compartments of a neuron are affected by Dimm to generate these morphological features...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28852096/a-multi-trap-microfluidic-chip-enabling-longitudinal-studies-of-nerve-regeneration-in-caenorhabditis-elegans
#5
Sertan Kutal Gokce, Evan Marley Hegarty, Sudip Mondal, Peisen Zhao, Navid Ghorashian, Massimo A Hilliard, Adela Ben-Yakar
Several sophisticated microfluidic devices have recently been proposed for femtosecond laser axotomy in the nematode C. elegans for immobilization of the animals for surgery to overcome time-consuming and labor-intensive manual processes. However, nerve regeneration studies require long-term recovery of the animals and multiple imaging sessions to observe the regeneration capabilities of their axons post-injury. Here we present a simple, multi-trap device, consisting of a single PDMS (polydimethylsiloxane) layer, which can immobilize up to 20 animals at the favorable orientation for optical access needed for precise laser surgery and high-resolution imaging...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851362/inverse-associations-between-serum-levels-of-secreted-frizzled-related-protein-5-sfrp5-and-multiple-cardiometabolic-risk-factors-kora-f4-study
#6
Maren Carstensen-Kirberg, Julia M Kannenberg, Cornelia Huth, Christa Meisinger, Wolfgang Koenig, Margit Heier, Annette Peters, Wolfgang Rathmann, Michael Roden, Christian Herder, Barbara Thorand
AIMS: Secreted frizzled-related protein (Sfrp)5 has beneficial effects on insulin sensitivity, inflammation and cardiovascular risk in different mouse models, but its relevance for cardiometabolic diseases in humans is controversial. We aimed to characterise associations of circulating SFRP5 with cardiometabolic risk factors and prediabetes/type 2 diabetes in a large population-based cohort. METHODS: Cross-sectional associations between serum SFRP5 and cardiometabolic risk factors as well as prediabetes/type 2 diabetes were investigated in 1096 participants aged 62-81 years from the German KORA F4 study, of whom 666 had prediabetes or type 2 diabetes...
August 29, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28840375/frizzled-5-a-high-affinity-receptor-for-secreted-frizzled-related-protein-2-activation-of-nuclear-factor-of-activated-t-cells-c3-signaling-to-promote-angiogenesis
#7
Yuri K Peterson, Patrick Nasarre, Ingrid V Bonilla, Eleanor Hilliard, Jennifer Samples, Thomas A Morinelli, Elizabeth G Hill, Nancy Klauber-DeMore
Secreted frizzled-related protein 2 (SFRP2) is a pro-angiogenic factor expressed in the vasculature of a wide variety of human tumors, and modulates angiogenesis via the calcineurin-dependent nuclear factor of activated T-cells cytoplasmic 3 (NFATc3) pathway in endothelial cells. However, until now, SFRP2 receptor for this pathway was unknown. In the present study, we first used amino acid alignments and molecular modeling to demonstrate that SFRP2 interaction with frizzled-5 (FZD5) is typical of Wnt/FZD family members...
August 24, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28834606/secreted-frizzled-related-protein-5-protects-against-oxidative-stress-induced-apoptosis-in-human-aortic-endothelial-cells-via-downregulation-of-bax
#8
Xiaojie Wang, Qing Peng, Feng Jiang, Li Xue, Jiafu Li, Zhongcai Fan, Pan Chen, Guo Chen, Yihua Cai
This study was undertaken to determine the role of secreted frizzled-related protein 5 (SFRP5) in endothelial oxidative injury. Human aortic endothelial cells (HAECs) were exposed to different oxidative stimuli and examined for SFRP5 expression. The effects of SFRP5 overexpression and knockdown on cell viability, apoptosis, and reactive oxygen species production were measured. HAECs treated with angiotensin (Ang) II (1 μM) or oxidized low-density lipoprotein (oxLDL) (150 μg/mL) showed a significant increase in SFRP5 expression...
August 23, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28811361/chemoradiotherapy-resistance-in-colorectal-cancer-cells-is-mediated-by-wnt-%C3%AE-catenin-signaling
#9
Georg Emons, Melanie Spitzner, Sebastian Reineke, Janneke Möller, Noam Auslander, Frank Kramer, Yue Hu, Tim Beissbarth, Hendrik A Wolff, Margret Rave-Fränk, Elisabeth Heßmann, Jochen Gaedcke, B Michael Ghadimi, Steven A Johnsen, Thomas Ried, Marian Grade
Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer. The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy and TCF7L2 mediates resistance to chemoradiotherapy. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small-molecule inhibitor (XAV-939) resulted in sensitization of colorectal cancer cells to chemoradiotherapy...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28808056/the-crystal-structure-of-full-length-sizzled-from-xenopus-laevis-yields-insights-into-wnt-antagonistic-function-of-secreted-frizzled-related-proteins
#10
Qixin Bu, Zhiqiang Li, Junying Zhang, Fei Xu, Jianmei Liu, Heli Liu
The Wnt signaling pathway is crucial to cell proliferation, differentiation and migration. The secreted frizzled-related proteins (sFRPs) represent the largest family of secreted Wnt inhibitors. However, their function in antagonizing Wnt signaling has remained somewhat controversial. Here we report the crystal structure of Sizzled from Xenopus laevis, the first full-length structure of an sFRP. Tethered by an inter-domain disulfide bond and a linker, the N-terminal CRD domain and the C-terminal NTR domain of Sizzled are arranged in a tandem fashion, with the NTR domain occluding the groove of CRD for Wnt accessibility...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28807014/epigenetic-reprogramming-converts-human-wharton-s-jelly-mesenchymal-stem-cells-into-functional-cardiomyocytes-by-differential-regulation-of-wnt-mediators
#11
G Bhuvanalakshmi, Frank Arfuso, Alan Prem Kumar, Arun Dharmarajan, Sudha Warrier
BACKGROUND: Lineage commitment of mesenchymal stem cells (MSCs) to cardiac differentiation is controlled by transcription factors that are regulated by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Here, we studied the differentiation of human Wharton's jelly MSCs (WJMSCs) into the cardiomyocyte lineage via epigenetic manipulations. METHODS: We introduced these changes using inhibitors of DNA methyl transferase and histone deacetylase, DC301, DC302, and DC303, in various combinations...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28803732/reck-and-gpr124-are-essential-receptor-cofactors-for-wnt7a-wnt7b-specific-signaling-in-mammalian-cns-angiogenesis-and-blood-brain-barrier-regulation
#12
Chris Cho, Philip M Smallwood, Jeremy Nathans
Reck, a GPI-anchored membrane protein, and Gpr124, an orphan GPCR, have been implicated in Wnt7a/Wnt7b signaling in the CNS vasculature. We show here that vascular endothelial cell (EC)-specific reduction in Reck impairs CNS angiogenesis and that EC-specific postnatal loss of Reck, combined with loss of Norrin, impairs blood-brain barrier (BBB) maintenance. The most N-terminal domain of Reck binds to the leucine-rich repeat (LRR) and immunoglobulin (Ig) domains of Gpr124, and weakening this interaction by targeted mutagenesis reduces Reck/Gpr124 stimulation of Wnt7a signaling in cell culture and impairs CNS angiogenesis...
August 30, 2017: Neuron
https://www.readbyqxmd.com/read/28794794/sfrp2-enhances-the-osteogenic-differentiation-of-apical-papilla-stem-cells-by-antagonizing-the-canonical-wnt-pathway
#13
Luyuan Jin, Yu Cao, Guoxia Yu, Jinsong Wang, Xiao Lin, Lihua Ge, Juan Du, Liping Wang, Shu Diao, Xiaomeng Lian, Songlin Wang, Rui Dong, Zhaochen Shan
BACKGROUND: Exploring the molecular mechanisms underlying directed differentiation is helpful in the development of clinical applications of mesenchymal stem cells (MSCs). Our previous study on dental tissue-derived MSCs demonstrated that secreted frizzled-related protein 2 (SFRP2), a Wnt inhibitor, could enhance osteogenic differentiation in stem cells from the apical papilla (SCAPs). However, how SFRP2 promotes osteogenic differentiation of dental tissue-derived MSCs remains unclear...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28790854/hypermethylation-of-secreted-frizzled-related-proteins-predicts-poor-prognosis-in-non-m3-acute-myeloid-leukemia
#14
Hong Guo, Ting-Juan Zhang, Xiang-Mei Wen, Jing-Dong Zhou, Ji-Chun Ma, Cui An, Wei Zhang, Zi-Jun Xu, Jiang Lin, Jun Qian
OBJECTIVE: Secreted frizzled-related proteins (SFRPs) as Wnt signaling antagonists have been found to be dysregulated by promoter hypermethylation in several cancers including acute myeloid leukemia (AML). This study aimed to investigate the methylated status of SFRPs promoter region and its clinical relevance in Chinese non-M3 AML patients. METHODS: SFRPs methylation in 139 primary non-M3 AML patients was determined using methylation-specific real-time quantitative polymerase chain reaction...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790300/agonist-induced-dimer-dissociation-as-a-macromolecular-step-in-g-protein-coupled-receptor-signaling
#15
Julian Petersen, Shane C Wright, David Rodríguez, Pierre Matricon, Noa Lahav, Aviv Vromen, Assaf Friedler, Johan Strömqvist, Stefan Wennmalm, Jens Carlsson, Gunnar Schulte
G protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors. They can exist and act as dimers, but the requirement of dimers for agonist-induced signal initiation and structural dynamics remains largely unknown. Frizzled 6 (FZD6) is a member of Class F GPCRs, which bind WNT proteins to initiate signaling. Here, we show that FZD6 dimerizes and that the dimer interface of FZD6 is formed by the transmembrane α-helices four and five. Most importantly, we present the agonist-induced dissociation/re-association of a GPCR dimer through the use of live cell imaging techniques...
August 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28782472/canonical-microrna-matching-differs-greatly-across-groups-of-g-protein-coupled-receptor-mrnas
#16
Michael S Parker, Ambikaipakan Balasubramaniam, Floyd R Sallee, Steven L Parker
BACKGROUND: Heptahelical G protein coupled receptors (GPCRs) support numerous sensory and metabolic functions and differ considerably in levels of expression. GPCR protein levels should link to regulation of GPCR mRNAs by microRNAs (miRs), which might significantly depend on numbers, size and GC content of the canonical antisense matches in mRNAs. These parameters of GPCR mRNAs have not been studied in detail. METHODS: Canonical matching profiles of human GPCR mRNAs and miRs were examined using segments of 7-15 nucleotides in windows shifted by one position over the entire microRNA sequence...
August 4, 2017: MicroRNA
https://www.readbyqxmd.com/read/28777432/comparison-of-a-prototype-reverse-hybridization-assay-and-methylight-for-detection-of-sfrp2-promotor-methylation-in-fecal-dna
#17
Gernot Kriegshäuser, Dietmar Enko, Matthias Zitt, Michael Oberwalder, Christian Oberkanins, Dietmar Öfner, Robert Zeillinger, Hannes Maximilian Müller
BACKGROUND: This study aimed to evaluate the diagnostic performance of a novel nonquantitative methylation-specific reverse hybridization (MSRH) assay to detect secreted frizzled-related protein 2 (SFRP2) promotor methylation in fecal DNA. METHODS: SFRP2 promoter methylation was investigated in stool DNA isolated from 18 colorectal cancer (CRC) patients and 22 healthy controls using the MSRH assay based on methylation-specific DNA amplification followed by reverse hybridization of biotinylated amplicons to sequence-specific methylation detection probes, with MethyLight serving as a reference method...
July 26, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28772260/microrna-27a-promotes-the-proliferation-and-invasiveness-of-colon-cancer-cells-by-targeting-sfrp1-through-the-wnt-%C3%AE-catenin-signaling-pathway
#18
Sang Ba, Yi Xuan, Zi-Wen Long, Hai-Yong Chen, Shu-Sen Zheng
OBJECTIVE: This study aims to explore the effects of microRNA-27a (miR-27a) on the proliferation and invasiveness of colon cancer cells through the Secreted Frizzled-related protein 1 (SFRP1) and the Wnt/β-catenin signaling pathway. METHODS: Colon cancer tissues and adjacent normal tissues from 125 colon cancer patients, together with the HCEpic, HCT-116, HT-29, SW480 and SW620 cell lines, were prepared for this study. The transfected HCT-116 cells were divided into the miR-27a mimics, miR-27a-NC, anti-miR-27a, blank, Lv-SFRP1, Lv-NC, and miR-27a mimics + Lv-SFRP1 groups...
August 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28754856/overexpression-of-mir-135b-5p-promotes-unfavorable-clinical-characteristics-and-poor-prognosis-via-the-repression-of-sfrp4-in-pancreatic-cancer
#19
Xu Han, Hexige Saiyin, Junjie Zhao, Yuan Fang, Yefei Rong, Chenye Shi, Wenhui Lou, Tiantao Kuang
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and malignant neoplasm. The aberrant expression of miR-135b-5p and secreted frizzled-related protein 4 (SFRP4) has been revealed to be involved in various cancers. However, the clinical significance of miR-135b-5p and that of its potential target SFRP4 in PDAC remain to be elucidated. Here, we found that miR-135b-5p was markedly upregulated in pancreatic cancer tissue compared with corresponding adjacent normal tissue, whereas SFRP4 was significantly downregulated...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28752891/inhibition-of-nuclear-wnt-signaling-challenges-of-an-elusive-target-for-cancer-therapy
#20
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
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