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https://www.readbyqxmd.com/read/29777010/developmental-vascular-regression-is-regulated-by-a-wnt-%C3%AE-catenin-myc-p21-cdkn1a-pathway-that-controls-cell-proliferation-and-cell-death
#1
Gowri Nayak, Yoshinobu Odaka, Vikram Prasad, Alyssa F Solano, Eun-Jin Yeo, Shruti Vemaraju, Jeffery D Molkentin, Andreas Trumpp, Bart Williams, Sujata Rao, Richard A Lang
Normal development requires tight regulation of cell proliferation and cell death. Here, we investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/β-catenin response for scheduled regression. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc , and the cyclin-dependent kinase inhibitor P21 (CDKN1A), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway coreceptors LRP5 and LRP6 have overlapping activities mediating the Wnt/β-catenin signaling in hyaloid vascular endothelial cells (VECs)...
May 18, 2018: Development
https://www.readbyqxmd.com/read/29718273/fgf23-regulates-wnt-%C3%AE-catenin-signaling-mediated-osteoarthritis-in-mice-overexpressing-high-molecular-weight-fgf2
#2
Patience Meo Burt, Liping Xiao, Marja M Hurley
Although humans with X-linked hypophosphatemia (XLH) and the Hyp mouse, a murine homologue of XLH, are known to develop degenerative joint disease, the exact mechanism which drives the osteoarthritic (OA) phenotype remains unclear. Mice that overexpress high molecular weight FGF2 isoforms (HMWTg mice) phenocopy both XLH and Hyp including OA with increased fibroblast growth factor 23 (FGF23) production in bone and serum. Since HMWTg cartilage also has increased FGF23 and there is crosstalk between FGF23-Wnt/β-catenin signaling, the purpose of this study was to determine if OA observed in HMWTg mice is due to FGF23 mediated-canonical Wnt signaling in chondrocytes given that both pathways are implicated in OA pathogenesis...
April 26, 2018: Endocrinology
https://www.readbyqxmd.com/read/29691731/evaluating-the-potential-of-housekeeping-genes-rrnas-snrnas-micrornas-and-circrnas-as-reference-genes-for-the-estimation-of-pmi
#3
Chunyan Tu, Tieshuai Du, Chengchen Shao, Zengjia Liu, Liliang Li, Yiwen Shen
The precise estimation of postmortem interval (PMI) is a critical step in death investigation of forensic cases. Detecting the degradation of RNA in tissues by real time quantitative polymerase chain reaction (RT-qPCR) technology provides a new theoretical basis for estimation of PMI. However, most commonly used reference genes degrade over time, while previous studies seldom consider this when selecting suitable reference genes for the estimation of PMI. Studies have shown microRNAs (miRNAs) are very stable and circular RNAs (circRNAs) have recently emerged as a novel class of RNAs with high stability...
April 24, 2018: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/29665441/nanorod-diameter-modulated-osteogenic-activity-of-hierarchical-micropore-nanorod-patterned-coatings-via-a-wnt-%C3%AE-catenin-pathway
#4
Jianhong Zhou, Lingzhou Zhao, Bo Li, Yong Han
Hierarchical micropore/nanorod-patterned strontium doped hydroxyapatite (Ca9 Sr1 (PO4 )6 (OH)2 , Sr1 -HA) structures (MNRs) with different nanorod diameters of about 30, 70 and 150 nm were coated on titanium, to investigate the effect of nanorod diameter on osteogenesis and the involved mechanism. Compared to micropore/nanogranule-patterned Sr1 -HA coating (MNG), MNRs gave rise to dramatically enhanced in vitro mesenchymal stem cell functions including osteogenic differentiation in the absence of osteogenic supplements and in vivo osseointegration related to the nanorod diameter with about 70 nm displaying the best effects...
April 14, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29662192/capillary-morphogenesis-gene-2-maintains-gastric-cancer-stem-like-cell-phenotype-by-activating-a-wnt-%C3%AE-catenin-pathway
#5
Chengdong Ji, Lang Yang, Weijing Yi, Dongfang Xiang, Yanxia Wang, Zhihua Zhou, Feng Qian, Yong Ren, Wei Cui, Xia Zhang, Peng Zhang, Ji Ming Wang, Youhong Cui, Xiuwu Bian
A growing body of evidence shows that the development and progression of gastric cancer (GC) is mainly associated to the presence of gastric cancer stem-like cells (GCSLCs). However, it is unclear how GCSLC population is maintained. This study aimed to explore the role of capillary morphogenesis gene 2 (CMG2) in GCSLC maintenance and the relevance to GC progression. We found that CMG2 was highly expressed in GC tissues and the expression levels were associated with the invasion depth and lymph node metastasis of GC, and inversely correlated with the survival of GC patients...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29659741/formin-2-regulates-lysosomal-degradation-of-wnt-associated-%C3%AE-catenin-in-neural-progenitors
#6
Gewei Lian, Anjen Chenn, Victor Ekuta, Sneha Kanaujia, Volney Sheen
Although neural progenitor proliferation along the ventricular zone is regulated by β-catenin through Wnt signaling, the cytoskeletal mechanisms that regulate expression and localization of these proteins are not well understood. Our prior studies have shown that loss of the actin-binding Filamin A (FlnA) and actin-nucleating protein Formin 2 (Fmn2) impairs endocytosis of low-density-lipoprotein-receptor-related protein 6 (Lrp6), thereby disrupting β-catenin activation, resulting in decreased brain size. Here, we report that activated RhoA-GTPase disengages Fmn2 N- to C-terminal binding to promote Fmn2 activation and redistribution into lysosomal vesicles...
April 5, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29656209/phosphorylation-of-low-density-lipoprotein-receptor-related-protein-6-is-involved-in-receptor-for-advanced-glycation-end-product-mediated-%C3%AE-catenin-stabilization-in-a-toluene-diisocyanate-induced-asthma-model
#7
Jing Xiong, Wenqu Zhao, Yun Lin, Lihong Yao, Guohua Huang, Changhui Yu, Hangming Dong, Guanhua Xiao, Haijin Zhao, Shaoxi Cai
BACKGROUND: We have previously demonstrated that the receptor for advanced glycation end products (RAGE)/β-catenin axis plays a vital role in regulating airway inflammation and airway remodeling in a toluene diisocyanate (TDI)-induced murine asthma model. However, the exact mechanism of β-catenin activation remains unclear. Given that phosphorylation of the low-density lipoprotein receptor-related protein 6 (Lrp6) is a key step in mediating β-catenin stabilization in canonical wnt/β-catenin signaling, we explored the possible relationship between RAGE and Lrp6 in regulating β-catenin stabilization in TDI-induced asthma...
April 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29626090/a-gtpase-activating-protein-binding-protein-g3bp1-antiviral-protein-relay-conveys-arteriosclerotic-wnt-signals-in-aortic-smooth-muscle-cells
#8
Bindu Ramachandran, John N Stabley, Su-Li Cheng, Abraham S Behrmann, Austin Gay, Li Li, Megan Mead, Julia Kozlitina, Andrew Lemoff, Hamid Mirzaei, Zhijian Chen, Dwight A Towler
In aortic vascular smooth muscle (VSM), the canonical Wnt receptor LRP6 inhibits protein arginine (Arg) methylation, a new component of noncanonical Wnt signaling that stimulates nuclear factor of activated T cells (viz., NFATc4). To better understand how methylation mediates these actions, mass spectrometry was performed on VSM cell extracts from control and LRP6-deficient mice. LRP6-dependent Arg methylation was regulated on > 500 proteins; only 21 exhibited increased monomethylation (MMA) with concomitant reductions in dimethylation...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29599839/rapamycin-protects-against-paraquat-induced-pulmonary-epithelial-mesenchymal-transition-via-the-wnt-%C3%AE-catenin-signaling-pathway
#9
Chanthasone Vongphouttha, Jie Zhu, Shuhao Deng, Wenlin Tai, Wenjuan Wu, Zhenkun Li, Wen Lei, Yin Wang, Zhaoxing Dong, Tao Zhang
Paraquat (PQ) is a herbicide that is widely used in developing countries, and pulmonary fibrosisis one of the most typical features of PQ poisoning. The molecular mechanism underlying PQ toxicity is largely unknown, which makes it difficult to treat. In the present study, western blot analysis, reverse transcription-quantitative polymerase chain reaction and fluorescent immunostaining were used to analyze the effects of rapamycin on PQ-induced epithelial-mesenchymal transition (EMT) in A549 and MRC-5 cells...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29579075/effects-of-pharmacologic-sclerostin-inhibition-or-testosterone-administration-on-soleus-muscle-atrophy-in-rodents-after-spinal-cord-injury
#10
Ean G Phillips, Luke A Beggs, Fan Ye, Christine F Conover, Darren T Beck, Dana M Otzel, Payal Ghosh, Anna C F Bassit, Stephen E Borst, Joshua F Yarrow
Sclerostin is a circulating osteocyte-derived glycoprotein that negatively regulates Wnt-signaling after binding the LRP5/LRP6 co-receptors. Pharmacologic sclerostin inhibition produces bone anabolic effects after spinal cord injury (SCI), however, the effects of sclerostin-antibody (Scl-Ab) on muscle morphology remain unknown. In comparison, androgen administration produces bone antiresorptive effects after SCI and some, but not all, studies have reported that testosterone treatment ameliorates skeletal muscle atrophy in this context...
2018: PloS One
https://www.readbyqxmd.com/read/29554480/osteogenesis-potential-of-different-titania-nanotubes-in-oxidative-stress-microenvironment
#11
Yonglin Yu, Xinkun Shen, Zhong Luo, Yan Hu, Menghuan Li, Pingping Ma, Qichun Ran, Liangliang Dai, Ye He, Kaiyong Cai
Oxidative stress is commonly existed in bone degenerative disease (osteoarthritis, osteoporosis etc.) and some antioxidants had great potential to enhance osteogenesis. In this study, we aim to investigate the anti-oxidative properties of various TiO2 nanotubes (TNTs) so to screen the desirable size for improved osteogenesis and reveal the underlying molecular mechanism in vitro. Comparing cellular behaviors under normal and oxidative stress conditions, an interesting conclusion was obtained. In normal microenvironment, small TNTs were beneficial for adhesion and proliferation of osteoblasts, but large TNTs greatly increased osteogenic differentiation...
March 13, 2018: Biomaterials
https://www.readbyqxmd.com/read/29524275/mutations-in-the-fourth-%C3%AE-propeller-domain-of-lrp4-are-associated-with-isolated-syndactyly-with-fusion-of-the-third-and-fourth-fingers
#12
Rivka Sukenik Halevy, Huan-Chieh Chien, Bo Heinz, Michael J Bamshad, Deborah A Nickerson, Martin Kircher, Nadav Ahituv
Isolated hand syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover two novel variants, chr11 g.46896373C>G; p.D1403H and chr11 g.46893078G>T; p.Q1564K, in LRP4 in a child with isolated bilateral syndactyly of the third and fourth fingers. Each variant was inherited from a different parent and neither parent was affected. Variants in LRP4 have been previously associated with syndactyly in Cenani-Lenz syndactyly syndrome and Sclerosteosis 2, but have not been reported in individuals with isolated syndactyly...
March 10, 2018: Human Mutation
https://www.readbyqxmd.com/read/29500247/whole-exome-sequencing-identifies-mutations-in-10-of-patients-with-familial-non-syndromic-cleft-lip-and-or-palate-in-genes-mutated-in-well-known-syndromes
#13
Mirta Basha, Bénédicte Demeer, Nicole Revencu, Raphael Helaers, Stephanie Theys, Sami Bou Saba, Odile Boute, Bernard Devauchelle, Geneviève Francois, Bénédicte Bayet, Miikka Vikkula
BACKGROUND: Oral clefts, that is, clefts of the lip and/or cleft palate (CL/P), are the most common craniofacial birth defects with an approximate incidence of ~1/700. To date, physicians stratify patients with oral clefts into either syndromic CL/P (syCL/P) or non-syndromic CL/P (nsCL/P) depending on whether the CL/P is associated with another anomaly or not. In general, patients with syCL/P follow Mendelian inheritance, while those with nsCL/P have a complex aetiology and, as such, do not adhere to Mendelian inheritance...
March 2, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29445127/cripto-1-contributes-to-stemness-in-hepatocellular-carcinoma-by-stabilizing-dishevelled-3-and-activating-wnt-%C3%AE-catenin-pathway
#14
Regina Cheuk-Lam Lo, Carmen Oi-Ning Leung, Kristy Kwan-Shuen Chan, Daniel Wai-Hung Ho, Chun-Ming Wong, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness...
February 14, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29444668/gigantol-inhibits-wnt-%C3%AE-catenin-signaling-and-exhibits-anticancer-activity-in-breast-cancer-cells
#15
Shubin Yu, Zhongyuan Wang, Zijie Su, Jiaxing Song, Liang Zhou, Qi Sun, Shanshan Liu, Shiyue Li, Ying Li, Meina Wang, Guo-Qiang Zhang, Xue Zhang, Zhong-Jian Liu, Desheng Lu
BACKGROUND: Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has been shown to have promising therapeutic potential against cancer cells, but its mechanism of action remains unclear. METHODS: The inhibitory effect of gigantol on Wnt/β-catenin signaling was evaluated with the SuperTOPFlash reporter system. The levels of phosphorylated low-density lipoprotein receptor related protein 6 (LRP6), total LRP6 and cytosolic β-catenin were determined by Western blot analysis...
February 14, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29439617/low-density-lipoprotein-receptor-related-protein-6-is-essential-for-trophoblast-survival-and-invasion
#16
Lei Li, Jipeng Wan, Jing Xue, Hongyan Li, Shan Wang, Qian Zhou, Yu Zhou, Xietong Wang
Remodeling of maternal spiral artery after the implantation of embryo relies on tightly regulated trophoblast functions and is pivotal to ensure the success of pregnancy. Low-density lipoprotein receptor-related protein 6 (LRP6) is implicated in angiogenesis and several vascular diseases, but its function in trophoblast regulation is still not fully understood. We aimed to investigate the involvement of LRP6 in trophoblast functions during maternal spiral artery remodeling. HTR-8/SVneo cells, a trophoblast cell line, were employed to examine the impact of LRP6 knockdown on proliferation, apoptosis, and migration, as well as invasion and tube formation...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29431745/dkk2-imparts-tumor-immunity-evasion-through-%C3%AE-catenin-independent-suppression-of-cytotoxic-immune-cell-activation
#17
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
March 2018: Nature Medicine
https://www.readbyqxmd.com/read/29414668/garcinol-inhibits-cancer-stem-cell-like-phenotype-via-suppression-of-the-wnt-%C3%AE-catenin-stat3-axis-signalling-pathway-in-human-non-small-cell-lung-carcinomas
#18
Wen-Chien Huang, Kuang-Tai Kuo, Bamodu Oluwaseun Adebayo, Chun-Hua Wang, Yu-Jen Chen, Ketao Jin, Tung-Hu Tsai, Chi-Tai Yeh
Innate or acquired drug resistance and consequent tumor relapse in lung cancer patients have been linked to activities of cancer stem cells (CSCs). Therefore, targeting CSCs is suggested as an effective approach for non-small cell lung cancer (NSCLC) therapy. In this study, we demonstrated that garcinol, a polyisoprenylated benzophenone isolated from fruiting bodies of Garcinia indica, and possessing anti-inflammatory, antioxidant, acetyltransferase inhibitory, and anticancer activities, modulates activities of lung CSCs (LCSCs) and their associated aggressiveness...
April 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29413898/lrp6-is-a-target-of-the-pth-activated-%C3%AE-nac-transcriptional-coregulator
#19
Martin Pellicelli, Hadla Hariri, Julie A Miller, René St-Arnaud
In the nucleus of differentiated osteoblasts, the alpha chain of nascent polypeptide associated complex (αNAC) interacts with cJUN transcription factors to regulate the expression of target genes, including Osteocalcin (Bglap2). PTH induces the phosphorylation of αNAC on serine 99 through a Gαs-PKA dependent pathway. This leads to activation of αNAC and expression of Bglap2. To identify additional target genes regulated by PTH-activated αNAC, we performed ChIP-Seq against αNAC in PTH-treated MC3T3-E1 cells...
February 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29408853/axin-phosphorylation-in-both-wnt-off-and-wnt-on-states-requires-the-tumor-suppressor-apc
#20
Ofelia Tacchelly-Benites, Zhenghan Wang, Eungi Yang, Hassina Benchabane, Ai Tian, Michael P Randall, Yashi Ahmed
The aberrant activation of Wnt signal transduction initiates the development of 90% of colorectal cancers, the majority of which arise from inactivation of the tumor suppressor Adenomatous polyposis coli (APC). In the classical model for Wnt signaling, the primary role of APC is to act, together with the concentration-limiting scaffold protein Axin, in a "destruction complex" that directs the phosphorylation and consequent proteasomal degradation of the transcriptional activator β-catenin, thereby preventing signaling in the Wnt-off state...
February 2018: PLoS Genetics
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