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https://www.readbyqxmd.com/read/29748286/structural-basis-for-recognition-of-frizzled-proteins-by-clostridium-difficile-toxin-b
#1
Peng Chen, Liang Tao, Tianyu Wang, Jie Zhang, Aina He, Kwok-Ho Lam, Zheng Liu, Xi He, Kay Perry, Min Dong, Rongsheng Jin
Clostridium difficile infection is the most common cause of antibiotic-associated diarrhea in developed countries. The major virulence factor, C. difficile toxin B (TcdB), targets colonic epithelia by binding to the frizzled (FZD) family of Wnt receptors, but how TcdB recognizes FZDs is unclear. Here, we present the crystal structure of a TcdB fragment in complex with the cysteine-rich domain of human FZD2 at 2.5-angstrom resolution, which reveals an endogenous FZD-bound fatty acid acting as a co-receptor for TcdB binding...
May 11, 2018: Science
https://www.readbyqxmd.com/read/29743880/-trypanosoma-cruzi-exploits-wnt-signaling-pathway-to-promote-its-intracellular-replication-in-macrophages
#2
Ximena Volpini, Laura F Ambrosio, Laura Fozzatti, Constanza Insfran, Cinthia C Stempin, Laura Cervi, Claudia Cristina Motran
During the acute phase of Trypanosoma cruzi infection, macrophages can act as host cells for the parasites as well as effector cells in the early anti-parasitic immune response. Thus, the targeting of specific signaling pathways could modulate macrophages response to restrict parasite replication and instruct an appropriate adaptive response. Recently, it has become evident that Wnt signaling has immunomodulatory functions during inflammation and infection. Here, we tested the hypothesis that during T. cruzi infection, the activation of Wnt signaling pathway in macrophages plays a role in modulating the inflammatory/tolerogenic response and therefore regulating the control of parasite replication...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29738529/identifying-novel-strategies-for-treating-human-hair-loss-disorders-cyclosporine-a-suppresses-the-wnt-inhibitor-sfrp1-in-the-dermal-papilla-of-human-scalp-hair-follicles
#3
Nathan J Hawkshaw, Jonathan A Hardman, Iain S Haslam, Asim Shahmalak, Amos Gilhar, Xinhong Lim, Ralf Paus
Hair growth disorders often carry a major psychological burden. Therefore, more effective human hair growth-modulatory agents urgently need to be developed. Here, we used the hypertrichosis-inducing immunosuppressant, Cyclosporine A (CsA), as a lead compound to identify new hair growth-promoting molecular targets. Through microarray analysis we identified the Wnt inhibitor, secreted frizzled related protein 1 (SFRP1), as being down-regulated in the dermal papilla (DP) of CsA-treated human scalp hair follicles (HFs) ex vivo...
May 2018: PLoS Biology
https://www.readbyqxmd.com/read/29730658/differential-patterns-of-secreted-frizzled-related-protein-4-sfrp4-in-adipocyte-differentiation-adipose-depot-specificity
#4
Hua Guan, Yali Zhang, Shoucui Gao, Liang Bai, Sihai Zhao, Xian Wu Cheng, Jianglin Fan, Enqi Liu
BACKGROUND/AIMS: Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that acts as soluble modulators of Wnt signaling. Given the substantial rise in obesity, depot-specific fat accumulation and its associated diseases like diabetes, it is important to understand the molecular basis of depot-specific adipocyte differentiation. In the current study, we investigated the expression of SFRP4 in both subcutaneous and visceral adipose tissue in terms of their differentiation...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29717114/frizzled-8-integrates-wnt-11-and-transforming-growth-factor-%C3%AE-signaling-in-prostate-cancer
#5
Virginia Murillo-Garzón, Irantzu Gorroño-Etxebarria, Malin Åkerfelt, Mikael Christer Puustinen, Lea Sistonen, Matthias Nees, James Carton, Jonathan Waxman, Robert M Kypta
Wnt-11 promotes cancer cell migration and invasion independently of β-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD8 is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-β signals to promote EMT. FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo. Analysis of patient samples reveals increased levels of FZD8 in cancer, correlating with Wnt-11. FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription...
May 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29704505/research-on-epigenetic-mechanism-of-sfrp2-in-advanced-chronic-myeloid-leukemia
#6
Ziye Li, Jianmin Luo
Secreted frizzled-related protein 2 (SFRP2) has been reported to act as a tumor suppressors. This study aims to detect the biological role of SFRP2 in advanced chronic myeloid leukemia (CML). In this study we examined bone marrow samples from 45 CML patients and 10 healthy donors. K562 and KCL22 cells were cultured and treated with demethylation drug and histone deacetylase inhibitor (HDACi). KCL22 and K562 cells were transfected with lentiviral vector (LV)-SFRP2, LV-control. The cells were then subjected to proliferation and apoptosis assays, real time polymerase chain reaction (PCR), Methylation-specific PCR (MSP), Western blotting, co-immunoprecipitation (CoIP) and Chromatin immunoprecipitation (ChIP), We found that SFRP2 was down-regulated in the accelerated and blast phase of CML, whereas, the levels of WNT1, WNT3 and WNT5A were up-regulated in the accelerated and blast phase of CML...
April 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29694926/gh-prevents-adipogenic-differentiation-of-mesenchymal-stromal-stem-cells-derived-from-human-trabecular-bone-via-canonical-wnt-signaling
#7
Simona Bolamperti, Michela Signo, Alice Spinello, GianLuigi Moro, Gianfranco Fraschini, Francesca Guidobono, Alessandro Rubinacci, Isabella Villa
The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA)...
April 22, 2018: Bone
https://www.readbyqxmd.com/read/29694885/wnt-signaling-mediates-ltp-dependent-spine-plasticity-and-ampar-localization-through-frizzled-7-receptors
#8
Faye McLeod, Alessandro Bossio, Aude Marzo, Lorenza Ciani, Sara Sibilla, Saad Hannan, Gemma A Wilson, Ernest Palomer, Trevor G Smart, Alasdair Gibb, Patricia C Salinas
The structural and functional plasticity of synapses is critical for learning and memory. Long-term potentiation (LTP) induction promotes spine growth and AMPAR accumulation at excitatory synapses, leading to increased synaptic strength. Glutamate initiates these processes, but the contribution from extracellular modulators is not fully established. Wnts are required for spine formation; however, their impact on activity-mediated spine plasticity and AMPAR localization is unknown. We found that LTP induction rapidly increased synaptic Wnt7a/b protein levels...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29649633/circulating-wnt-inhibitory-factor-1-levels-are-associated-with-development-of-cardiovascular-disease
#9
Claudia Ress, Mariya Paulweber, Georg Goebel, Karin Willeit, Kerstin Rufinatscha, Anna Strobl, Karin Salzmann, Ludmilla Kedenko, Alexander Tschoner, Gabriele Staudacher, Bernhard Iglseder, Herbert Tilg, Bernhard Paulweber, Susanne Kaser
BACKGROUND AND AIMS: Wnt signaling is involved in atherosclerotic plaque formation directly and indirectly by modulating cardiovascular risk factors. We investigated whether circulating concentrations of Wnt inhibitors are associated with cardiovascular events in subjects with intermediate cardiovascular risk. METHODS: 904 non-diabetic subjects participating in the SAPHIR study were assessed. In the SAPHIR study, middle-aged women without overt atherosclerotic disease at study entry were followed up for 10 years...
March 29, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29642895/wnt3a-ligand-facilitates-autophagy-in-hippocampal-neurons-by-modulating-a-novel-gsk-3%C3%AE-ampk-axis
#10
Juvenal A Ríos, Juan A Godoy, Nibaldo C Inestrosa
BACKGROUND: In the adult central nervous system (CNS), Wnt signaling regulates dendritic structure and synaptic plasticity. The Wnt signaling pathway can be divided into the canonical (β-catenin-dependent) and non-canonical pathways. In the canonical pathway, the binding of canonical ligands such as Wnt3a to the Frizzled receptor induces inactivation of glycogen synthase kinase-3β (GSK-3β), which stabilizes β-catenin and allows its translocation to the nucleus. However, to date, few studies have focused on β-catenin-independent Wnt signaling or explained the underlying mechanisms connecting Wnt signaling to cellular energy metabolism...
April 11, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29621541/kr%C3%A3-ppel-like-factor-9-suppressed-tumorigenicity-of-the-pancreatic-ductal-adenocarcinoma-by-negatively-regulating-frizzled-5
#11
Peiyu Ji, Xin Fan, Xiaoyan Ma, Xuqing Wang, Jianxin Zhang, Zhengfa Mao
Krüppel-like factor 9 (KLF9) has been implicated in mediating a diverse range of biological processes. However, the expression pattern and biological functions of KLF9 in pancreatic ductal adenocarcinoma (PDAC) are still unknown. Here, we evaluated the role of KLF9 in pancreatic ductal adenocarcinoma (PDAC). Overexpression of KLF9 significantly inhibited proliferation and clone formation in PDAC cells, while silencing KLF9 expression dramatically promoted this effect in vitro. Knocking down the expression of KLF9 also promoted the tumorigenesis in the PDAC mouse xneograft model...
April 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29620167/decreased-expression-of-sfrp2-promotes-development-of-the-pituitary-corticotroph-adenoma-by-upregulating-wnt-signaling
#12
Jie Ren, Fangfang Jian, Hong Jiang, Yuhao Sun, Sijian Pan, Changwei Gu, Xiao Chen, Weiqing Wang, Guang Ning, Liuguan Bian, Qingfang Sun
Cushing's disease is primarily caused by pituitary adrenocorticotropin‑secreting adenoma. However, its pathogenesis has remained obscure. In the present study, whole transcriptome analysis was performed by RNA sequencing (RNA‑Seq) and expression of secreted frizzled‑related protein 2 (SFRP2) was decreased in corticotroph tumors compared with normal pituitary glands. Furthermore, the RNA‑Seq results were validated and the expression of SFRP2 in tumor tissues was analyzed by comparing another cohort of 23 patients with Cushing's disease and 3 normal human pituitary samples using reverse transcription‑quantitative polymerase chain reaction, western blot and immunohistochemistry staining...
April 3, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29619545/morphological-and-molecular-characterization-of-the-senile-osteoporosis-in-senescence-accelerated-mouse-prone-6-samp6
#13
REVIEW
Kagaku Azuma, Qian Zhou, Kin-Ya Kubo
Although the understanding of the complex pathogenesis for osteoporosis is appreciable, the underlying mechanism is not yet fully elucidated. There is a great need to further characterize the available animal models in osteoporosis research. The senescence-accelerated mouse prone 6 (SAMP6) mice have been developed as the spontaneous experimental model for senile osteoporosis. Here, we provide a comprehensive overview of current research regarding the bone morphological and molecular alterations and the possible mechanisms involved in these changes...
April 4, 2018: Medical Molecular Morphology
https://www.readbyqxmd.com/read/29615567/the-roles-of-the-wnt-antagonists-axin-and-lrp4-during-embryogenesis-of-the-red-flour-beetle-tribolium-castaneum
#14
Romy Prühs, Anke Beermann, Reinhard Schröder
In both vertebrates and invertebrates, the Wnt-signaling pathway is essential for numerous processes in embryogenesis and during adult life. Wnt activity is fine-tuned at various levels by the interplay of a number of Wnt-agonists (Wnt ligands, Frizzled-receptors, Lrp5/6 coreceptors) and Wnt-antagonists (among them Axin, Secreted frizzled and Lrp4) to define anterior-posterior polarity of the early embryo and specify cell fate in organogenesis. So far, the functional analysis of Wnt-pathway components in insects has concentrated on the roles of Wnt-agonists and on the Wnt-antagonist Axin...
October 15, 2017: Journal of Developmental Biology
https://www.readbyqxmd.com/read/29610564/effects-of-secreted-frizzled-related-protein-1-on-proliferation-migration-invasion-and-apoptosis-of-colorectal-cancer-cells
#15
Zhongchuan Wang, Rujia Li, Yongshan He, Shiyong Huang
Background: Secreted frizzled-related protein 1 (SFRP1) is a member of the SFRPs family that modulates the Wnt signal transduction pathway. Recent studies have showed down-regulation of SFRP1 expression in colorectal cancer (CRC). We aimed to evaluate the effect of SFRP1 on the proliferation, migration, invasion and apoptosis of CRC cells in vitro. Materials and methods: We used real-time fluorescence quantification (RT-PCR) and Western blotting to detect SFRP1 expression in CRC, pericarcinomatous tissues and CRC cell lines...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29602811/identification-of-proteins-required-for-precise-positioning-of-apc2-in-dendrites
#16
Alexis T Weiner, Dylan Y Seebold, Nick L Michael, Michelle Guignet, Chengye Feng, Brandon Follick, Brandon A Yusko, Nathan P Wasilko, Pedro Torres-Gutierrez, Melissa M Rolls
In Drosophila neurons, uniform minus-end-out polarity in dendrites is maintained in part by kinesin-2-mediated steering of growing microtubules at branch points. Apc links the kinesin motor to growing microtubule plus ends and Apc2 recruits Apc to branch points where it functions. Because Apc2 acts to concentrate other steering proteins to branch points, we wished to understand how Apc2 is targeted. From an initial broad candidate RNAi screen, we found Miro (a mitochondrial transport protein), Ank2, Axin, spastin and Rac1 were required to position Apc2-GFP at dendrite branch points...
March 30, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29588395/substratum-stiffness-tunes-proliferation-downstream-of-wnt3a-in-part-by-regulating-integrin-linked-kinase-and-frizzled-1
#17
Siyang Han, Mei-Fong Pang, Celeste M Nelson
The Wnt/β-catenin pathway controls a variety of cellular behaviors, aberrant activation of which are associated with tumor progression in several types of cancer. The same cellular behaviors are also affected by the mechanical properties of the extracellular matrix (ECM) substratum, which induces signaling through integrins and integrin-linked kinase (ILK). Here, we examined the role of substratum stiffness in the regulation of cell proliferation downstream of Wnt3a. We found that treatment with Wnt3a increased proliferation of cells cultured on stiff substrata, with compliances characteristic of breast tumors, but not of cells on soft substrata, with compliances comparable to that of normal mammary tissue...
March 27, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29579399/gsk3-activated-stat5-regulates-expression-of-sfrps-to-modulate-adipogenesis
#18
Li Wang, Yuan Wang, Yuan Meng, Chao Zhang, Lijun Di
Adipogenesis is a tightly regulated cellular process and is closely associated with obesity and its associated metabolic disorders, such as diabetes. Multiple transcription factors and signaling pathways are involved in the regulation of adipogenesis. Here, we report that glycogen synthase kinase (GSK3), which was reported to play an important role in many cellular processes, is essential to adipocyte differentiation at early and terminal differentiation phases. Mechanistically, GSK3 modulates adipogenesis through regulation of both canonical Wnt pathways, which involve Wnt/β-catenin signaling, and noncanonical Wnt pathways, which include JNK and Ras-related C3 botulinum toxin substrate signaling...
March 26, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29568900/glucosamine-promotes-chondrocyte-proliferation-via-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway
#19
Yuhuan Ma, Wenwei Zheng, Houhuang Chen, Xiang Shao, Pingdong Lin, Xianxiang Liu, Xihai Li, Hongzhi Ye
The present study investigated the mechanism underlying the effects of glucosamine (GlcN) on the proliferation of chondrocytes isolated from the knee cartilage of Sprague‑Dawley rats. Chondrocytes were treated with various concentrations of GlcN or without GlcN. The effects of GlcN on chondrocyte proliferation were determined using reverse transcription‑polymerase chain reaction, western blot analysis and immunohistochemistry. The results indicated that GlcN significantly improved chondrocyte viability, accelerated G1/S transition during progression of the cell cycle and promoted the expression of cell cycle regulatory proteins, including cyclin D1, cyclin‑dependent kinase (CDK)4 and CDK6, thus indicating that GlcN may promote chondrocyte proliferation...
March 22, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29566281/downregulation-of-mir-3127-5p-promotes-epithelial-mesenchymal-transition-via-fzd4-regulation-of-wnt-%C3%AE-catenin-signaling-in-non-small-cell-lung-cancer
#20
Yang Yang, Yifeng Sun, Yun Wu, Dongfang Tang, Xi Ding, Wen Xu, Bo Su, Wen Gao
MiR-3127-5p has been implicated as a tumor-suppressive microRNA (miRNA) in non-small-cell lung cancer (NSCLC) and its expression was associated with tumor recurrence and poor prognosis. The aim of this study was to determine whether miR-3127-5p regulates epithelial-mesenchymal transition (EMT) in NSCLC, and to investigate the underlying mechanisms. Using qRT-PCR, we examined the expression levels of miR-3127-5p in a cohort of primary NSCLC specimens with and without distant metastasis. We further performed a series of in vitro and in vivo experiments to investigate the effects and underlying mechanism of miR-3127-5p on EMT, cell migration, invasion and adhesion in NSCLC...
March 22, 2018: Molecular Carcinogenesis
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