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Wnt activators

Juliet Richetto, Renaud Massart, Ulrike Weber-Stadlbauer, Moshe Szyf, Marco A Riva, Urs Meyer
BACKGROUND: Prenatal exposure to infectious or inflammatory insults increases the risk of neurodevelopmental disorders. Using a well-established mouse model of prenatal viral-like immune activation, we examined whether this pathological association involves genome-wide DNA methylation differences at single nucleotide resolution. METHODS: Prenatal immune activation was induced by maternal treatment with the viral mimetic polyriboinosinic-polyribocytidylic acid in middle or late gestation...
August 12, 2016: Biological Psychiatry
Sajjad Karim, Jaudah A Al-Maghrabi, Hasan M A Farsi, Ahmad J Al-Sayyad, Hans-Juergen Schulten, Abdelbaset Buhmeida, Zeenat Mirza, Alaa A Al-Boogmi, Fai T Ashgan, Manal M Shabaad, Hend F NourEldin, Khalid B M Al-Ghamdi, Adel Abuzenadah, Adeel G A Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Renal cell carcinoma (RCC) is a seventh ranked malignancy with poor prognosis. RCC is lethal at metastatic stage as it does not respond to conventional systemic treatments, and there is an urgent need to find out promising novel biomarkers for effective treatment. The goal of this study was to evaluate the biomarkers that can be potential therapeutic target and predict effective inhibitors to treat the metastatic stage of RCC. METHODS: We conducted transcriptomic profiling to identify differentially expressed genes associated with RCC...
September 30, 2016: BMC Cancer
C Tsentidis, D Gourgiotis, L Kossiva, A Marmarinos, A Doulgeraki, K Karavanaki
: Higher levels of Dickkopf-1, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy. INTRODUCTION: Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D)...
October 20, 2016: Osteoporosis International
Soula Danopoulos, Michael Krainock, Omar Toubat, Matthew Thornton, Brendan Grubbs, Denise Al Alam
Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment and polarization. Furthermore, Rac1 modulates both non-canonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching...
October 7, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
J Y Wang, Y Xia, C C Yang, Z Wang
Objective: To analysis the important genes and functions of cochlear hair cells with oxidative stress injury, by the construction of gene regulatory network which based on different miRNA in cochlear hair cells in vitro with oxidative stress injury, and to explore the molecular mechanisms of deafness based on oxidative stress injury. Method: The oxidative stress damage cochlear hair cell model was induced by 200 μmol/L t-BHP exposure in vitro. Small RNA deep sequencing analyzed the difference expression of miRNA and contructed gene regulatory network by 6 most significant difference miRNA...
October 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
QiuShi Wei, Jin Zhang, GuoJu Hong, ZhenQiu Chen, WeiMin Deng, Wei He, Mei Hui Chen
Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Issei Egashira, Fumi Takahashi-Yanaga, Risa Nishida, Masaki Arioka, Kazunobu Igawa, Katsuhiko Tomooka, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Yusaku Nakabeppu, Takanari Kitazono, Toshiyuki Sasaguri
We previously reported that celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, strongly inhibited human colon cancer cell proliferation by suppressing the Wnt/β-catenin signaling pathway. 2,5-Dimethylcelecoxib (DM-celecoxib), a celecoxib analogue, which does not inhibit COX-2, has also been reported to have an anti-tumor effect. In the present study, we elucidated whether DM-celecoxib inhibits intestinal cancer growth, and its underlying mechanism of action. First, we compared the effect of DM-celecoxib with that of celecoxib on the human colon cancer cell lines HCT-116 and DLD-1...
October 20, 2016: Cancer Science
Marc N Wein, Yanke Liang, Olga Goransson, Thomas B Sundberg, Jinhua Wang, Elizabeth A Williams, Maureen J O'Meara, Nicolas Govea, Belinda Beqo, Shigeki Nishimori, Kenichi Nagano, Daniel J Brooks, Janaina S Martins, Braden Corbin, Anthony Anselmo, Ruslan Sadreyev, Joy Y Wu, Kei Sakamoto, Marc Foretz, Ramnik J Xavier, Roland Baron, Mary L Bouxsein, Thomas J Gardella, Paola Divieti-Pajevic, Nathanael S Gray, Henry M Kronenberg
Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2...
October 19, 2016: Nature Communications
Claire Peghaire, Marie Lise Bats, Raj Sewduth, Sylvie Jeanningros, Beatrice Jaspard, Thierry Couffinhal, Cécile Duplàa, Pascale Dufourcq
OBJECTIVE: Vessel formation requires precise orchestration of a series of morphometric and molecular events controlled by a multitude of angiogenic factors and morphogens. Wnt/frizzled signaling is required for proper vascular formation. In this study, we investigated the role of the Fzd7 (frizzled-7) receptor in retinal vascular development and its relationship with the Wnt/β-catenin canonical pathway and Notch signaling. APPROACH AND RESULTS: Using transgenic mice, we demonstrated that Fzd7 is required for postnatal vascular formation...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Yu Zou, Huei Jinn Tong, Mingming Li, Kai Soo Tan, Tong Cao
The ability of human embryonic stem cells (hESCs) to proliferate indefinitely is attributed to its high telomerase activity and associated long telomere. However, factors regulating telomere length in hESCs remain largely uncharacterized. The aims of this study were, to identify factors which modulate telomere length of hESCs, and to determine if the telomere length of hESCs influences cellular senescence of its differentiated progeny cells. Telomerase reverse transcriptase (TERT) gene expression, telomerase activity and telomere length of hESCs cultured in different culture systems were compared...
October 18, 2016: Biogerontology
Juan Wang, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
OBJECTIVE: Constitutive activation of Wnt/β-catenin pathway plays an important role in the pathogenesis of colon cancer; however, recent studies have also indicated that elevated Wnt levels are essential. In the present study, we investigated the potential role of (pro) renin receptor in the pathophysiology of colon cancer. DESIGN AND METHOD: (P) RR expression in human colon tissues was measured by immunohistochemistry and Western blot analysis. Human colon cancer cell lines DLD-1 with adenomatous polyposis coli (APC) truncated mutation, and HCT116 withβ-catenin activating mutation, were transfected with scramble siRNA and siRNA against (pro) renin receptor...
September 2016: Journal of Hypertension
Li Qin, Chan Liu, Ya-Guang Ni, Ya-Ning Shi, Bao-Xue Ao, Zheng Liu, Duan-Fang Liao
OBJECTIVE: Hypertension is closely associated with profound vascular remodeling, especially proliferation and hyperplasia of vascular smooth muscle cells (VSMCs). Aberrant Wnt5a signaling has been related to vascular diseases, but its role on the proliferation of VSMCs is unclear. The study evaluated the effect of Wnt5a on the proliferation of VSMCs and its possible mechanism. DESIGN AND METHOD: The capability of cell proliferation was detected by the assays of MTT, colony formation and EdU cell proliferation...
September 2016: Journal of Hypertension
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
Min-Jun Park, Ji-Hye Song, Myung-Soo Shon, Hae Ok Kim, O Jun Kwon, Seong-Soo Roh, Choon Young Kim, Gyo-Nam Kim
Obesity is a major risk factor for various metabolic diseases such as cardiovascular disease, hypertension, and type 2 diabetes mellitus. In this study, we prepared ethanol extracts from Agastache rugosa (ARE), Chrysanthemum zawadskii (CZE), Mentha arvensis (MAE), Perilla frutescens (PFE), Leonurus sibiricus (LSE), Gardenia jasminoides (GJE), and Lycopus coreanus (LCE). The anti-oxidant and anti-adipogenic effects were evaluated. The IC50 values for ascorbic acid and LCE against 2,2-diphenyl-1-picrylhydrazyl radicals were 246...
September 2016: Preventive Nutrition and Food Science
P-M Martin, R E Stanley, A P Ross, A E Freitas, C E Moyer, A C Brumback, J Iafrati, K S Stapornwongkul, S Dominguez, S Kivimäe, K A Mulligan, M Pirooznia, W R McCombie, J B Potash, P P Zandi, S M Purcell, S J Sanders, Y Zuo, V S Sohal, B N R Cheyette
Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/β-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls...
October 18, 2016: Molecular Psychiatry
Elissaveta Petrova, Arne Scholz, Juliane Paul, Andrea Sturz, Katja Haike, Franziska Siegel, Dominik Mumberg, Ningshu Liu
Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in de novo fatty acid synthesis, and its ACC1 isoform is overexpressed in pancreatic and various other cancers. The activity of many oncogenic signaling molecules, including WNT and Hedgehog (HH), is post-translationally modified by lipidation. Here, we report that inhibition of ACC by a small molecule inhibitor, BAY ACC002, blocked WNT3A lipidation, secretion, and signaling. In pancreatic cancer cells, where WNT and HH are key oncogenic drivers, ACC inhibition simultaneously suppressed WNT and HH signaling, and led to anti-proliferative effects...
October 13, 2016: Oncotarget
Olivier Boucherat, Kim Landry-Truchon, Rifdat Aoidi, Nicolas Houde, Valérie Nadeau, Jean Charron, Lucie Jeannotte
BACKGROUND: Reciprocal epithelial-mesenchymal communications are critical throughout lung development, dictating branching morphogenesis and cell specification. Numerous signaling molecules are involved in these interactions but how epithelial-mesenchymal crosstalk is coordinated remains unclear. The ERK/MAPK pathway transduces several important signals in lung formation. Epithelial inactivation of both Mek genes, encoding ERK/MAPK kinases, causes lung agenesis and death. Conversely, Mek mutation in mesenchyme results in lung hypoplasia, trachea cartilage malformations, kyphosis, omphalocele and death...
October 17, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Yoon Seob Kim, Kwan Ho Jeong, Jung Eun Kim, Young Jun Woo, Beom Joon Kim, Hoon Kang
BACKGROUND: Microneedle is a method that creates transdermal microchannels across the stratum corneum barrier layer of skin. No previous study showed a therapeutic effect of microneedle itself on hair growth by wounding. OBJECTIVE: The aim of this study is to investigate the effect of repeated microwound formed by microneedle on hair growth and hair growth-related genes in a murine model. METHODS: A disk microneedle roller was applied to each group of mice five times a week for three weeks...
October 2016: Annals of Dermatology
Ritva Heljasvaara, Mari Aikio, Heli Ruotsalainen, Taina Pihlajaniemi
Collagen XVIII is a ubiquitous basement membrane (BM) proteoglycan produced in three tissue-specific isoforms that differ in their N-terminal non-collagenous sequences, but share collagenous and C-terminal non-collagenous domains. The collagenous domain provides flexibility to the large collagen XVIII molecules on account of multiple interruptions in collagenous sequences. Each isoform has a complex multi-domain structure that endows it with an ability to perform various biological functions. The long isoform contains a frizzled-like (Fz) domain with Wnt-inhibiting activity and a unique domain of unknown function (DUF959), which is also present in the medium isoform...
October 13, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Melissa V Gammons, Trevor J Rutherford, Zachary Steinhart, Stephane Angers, Mariann Bienz
Dishevelled (DVL) assembles Wnt signalosomes through dynamic head-to-tail polymerisation by means of its DIX domain. It thus transduces Wnt signals to cytoplasmic effectors including β-catenin, to control cell fates during normal development, tissue homeostasis and also in cancer. To date, most functional studies of Dishevelled relied on its Wnt-independent signalling activity resulting from overexpression, which is sufficient to trigger polymerisation, bypassing the requirement for Wnt signals. Here, we generate a human cell line devoid of endogenous Dishevelled (DVL1- DVL3), which lacks Wnt signal transduction to β-catenin...
October 15, 2016: Journal of Cell Science
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