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https://www.readbyqxmd.com/read/28916299/non-canonical-wnt-mediated-neurogenic-differentiation-of-human-bone-marrow-derived-mesenchymal-stem-cells
#1
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/28852096/a-multi-trap-microfluidic-chip-enabling-longitudinal-studies-of-nerve-regeneration-in-caenorhabditis-elegans
#2
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/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
#3
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/28811361/chemoradiotherapy-resistance-in-colorectal-cancer-cells-is-mediated-by-wnt-%C3%AE-catenin-signaling
#4
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
#5
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
#6
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/28794794/sfrp2-enhances-the-osteogenic-differentiation-of-apical-papilla-stem-cells-by-antagonizing-the-canonical-wnt-pathway
#7
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
#8
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
#9
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/28772260/microrna-27a-promotes-the-proliferation-and-invasiveness-of-colon-cancer-cells-by-targeting-sfrp1-through-the-wnt-%C3%AE-catenin-signaling-pathway
#10
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
#11
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
#12
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/28737757/non-canonical-wnt-pcp-signalling-in-cancer-fzd6-takes-centre-stage
#13
REVIEW
G Corda, A Sala
Frizzled receptors are the mediators of the wnt canonical and non-canonical pathways, which play fundamental roles in cell differentiation and organism development. A large body of work indicates that dysregulation of wnt signalling is a feature of oncogenic transformation, but most of the studies published so far focus on the assessment of the consequences of aberrations of the canonical pathway in human cancer. In this review, we discuss the emerging role of the wnt non-canonical pathway regulated by frizzled receptor 6 (Fzd6) in the pathogenesis of different types of human malignancies...
July 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28736081/frizzled-7-mediates-tgf-%C3%AE-induced-pulmonary-fibrosis-by-transmitting-non-canonical-wnt-signaling
#14
Shuhong Guan, Jun Zhou
Pulmonary fibrosis is a progressive and often fatal lung disease characterized by fibroblast proliferation and excessive deposition of extracellular matrix. Both TGF-β and Wnt signaling have been implicated in the regulation of organ fibrosis. However little is known about whether TGF-β-induced gene expression changes in Wnt signaling pathway could predict disease progression. In the study, we investigated the interaction between TGF-β and Wnt signaling in mediating pulmonary fibrosis by big data analysis, in vitro and in vivo experimental studies and clinical data analysis...
July 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28733458/mapping-of-wnt-frizzled-interactions-by-multiplex-crispr-targeting-of-receptor-gene-families
#15
Oksana Voloshanenko, Philipp Gmach, Jan Winter, Dominique Kranz, Michael Boutros
Signaling pathway modules are often encoded by several closely related paralogous genes that can have redundant roles and are therefore difficult to analyze by loss-of-function analysis. A typical example is the Wnt signaling pathway, which in mammals is mediated by 19 Wnt ligands that can bind to 10 Frizzled (FZD) receptors. Although significant progress in understanding Wnt-FZD receptor interactions has been made in recent years, tools to generate systematic interaction maps have been largely lacking. Here we generated cell lines with multiplex mutant alleles of FZD1, FZD2, and FZD7 and demonstrate that these cells are unresponsive to canonical Wnt ligands...
July 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#16
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#17
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/28709873/deregulation-of-wnt2-fzd3-%C3%AE-catenin-pathway-compromises-the-estrogen-synthesis-in-cumulus-cells-from-patients-with-polycystic-ovary-syndrome
#18
Gu-Yuan Qiao, Bing-Wei Dong, Chao-Juan Zhu, Chang-You Yan, Bi-Liang Chen
Mechanistic insight into estrogen deficiency by polycystic ovary syndrome (PCOS) remains a longstanding challenge in reproductive medicine. Recent advance suggest that Wingless-type MMTV integration site family members (WNTs), in concert with its Frizzled (FZD) receptors, regulate normal folliculogenesis, luteogenesis and ovarian steroidogenesis. However, no studies have so far investigated any causality between WNT-FZDs interactions and disrupted estrogen synthesis under certain pathological conditions. Here, we show that (i) FZD3 expression was significantly up-regulated in the cumulus cells (CCs) from PCOS patients...
July 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28708837/extracellular-inhibitors-can-attenuate-tumorigenic-wnt-pathway-activity-in-adenomatous-polyposis-coli-mutants-predictions-of-a-validated-mathematical-model
#19
Gili Hochman, Karin Halevi-Tobias, Yuri Kogan, Zvia Agur
BACKGROUND: Despite considerable investigational efforts, no method to overcome the pathogenesis caused by loss of function (LoF) mutations in tumor suppressor genes has been successfully translated to the clinic. The most frequent LoF mutation in human cancers is Adenomatous polyposis coli (APC), causing aberrant activation of the Wnt pathway. In nearly all colon cancer tumors, the APC protein is truncated, but still retains partial binding abilities. OBJECTIVE & METHODS: Here, we tested the hypothesis that extracellular inhibitors of the Wnt pathway, although acting upstream of the APC mutation, can restore normal levels of pathway activity in colon cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28686724/dipeptidyl-peptidase-4-inhibitor-gemigliptin-protects-against-vascular-calcification-in-an-experimental-chronic-kidney-disease-and-vascular-smooth-muscle-cells
#20
Soon-Youn Choi, Hye-Myung Ryu, Eun-Joo Oh, Ji-Young Choi, Jang-Hee Cho, Chan-Duck Kim, Yong-Lim Kim, Sun-Hee Park
Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats...
2017: PloS One
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