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Wnt/b-catenin signal

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https://www.readbyqxmd.com/read/29438981/pgam5-released-from-damaged-mitochondria-induces-mitochondrial-biogenesis-via-wnt-signaling
#1
Dominic B Bernkopf, Kowcee Jalal, Martina Brückner, Karl X Knaup, Marc Gentzel, Alexandra Schambony, Jürgen Behrens
Mitochondrial abundance is dynamically regulated and was previously shown to be increased by Wnt/β-catenin signaling. Pgam5 is a mitochondrial phosphatase which is cleaved by the rhomboid protease presenilin-associated rhomboid-like protein (PARL) and released from membranes after mitochondrial stress. In this study, we show that Pgam5 interacts with the Wnt pathway component axin in the cytosol, blocks axin-mediated β-catenin degradation, and increases β-catenin levels and β-catenin-dependent transcription...
February 8, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29432728/galectin-3-is-essential-for-proper-bone-cell-differentiation-and-activity-bone-remodeling-and-biomechanical-competence-in-mice
#2
Carla Iacobini, Claudia Blasetti Fantauzzi, Rossella Bedini, Raffaella Pecci, Armando Bartolazzi, Bruno Amadio, Carlo Pesce, Giuseppe Pugliese, Stefano Menini
OBJECTIVE: Galectin-3 is constitutively expressed in bone cells and was recently shown to modulate osteogenic transdifferentiation of vascular smooth muscle cells and atherosclerotic calcification. However, the role of galectin-3 in bone physiology is largely undefined. To address this issue, we analyzed (1) the skeletal features of 1-, 3- and 6-month-old galectin-3 null (Lgals3-/-) and wild type (WT) mice and (2) the differentiation and function of osteoblasts and osteoclasts derived from these animals...
February 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29428562/notum-attenuates-wnt-%C3%AE-catenin-signaling-to-promote-tracheal-cartilage-patterning
#3
B Gerhardt, L Leesman, K Burra, J Snowball, Racheal Rosenzweig, Natalie Guzman, M Ambalavanan, D Sinner
Tracheobronchomalacia (TBM) is a common congenital disorder in which the cartilaginous rings of the trachea are weakened or missing. Despite the high prevalence and clinical issues associated with TBM, the etiology is largely unknown. Our previous studies demonstrated that Wntless (Wls) and its associated Wnt pathways are critical for patterning of the upper airways. Deletion of Wls in respiratory endoderm caused TBM and ectopic trachealis muscle. To understand mechanisms by which Wls mediates tracheal patterning, we performed RNA sequencing in prechondrogenic tracheal tissue of Wlsf/f;ShhCre/wt embryos...
February 8, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29428231/bcl9-upregulation-in-adrenocortical-carcinoma-a-novel-wnt-%C3%AE-catenin-activating-event-driving-adrenocortical-malignancy
#4
Taylor C Brown, Norman G Nicolson, Reju Korah, Tobias Carling
BACKGROUND: B-Cell CLL/Lymphoma 9 (BCL9) is a recently described oncogene that promotes tumorigenesis via activation of the Wnt/β-Catenin signaling cascade. Though constitutively active Wnt/β-Catenin signaling is a molecular hallmark of adrenocortical carcinoma (ACC), a potential role for BCL9 to promote Wnt/β-Catenin pathway dysregulation in adrenocortical tumorigenesis remains to be elucidated. STUDY DESIGN: This study involved a retrospective analysis at a tertiary academic referral center of 27 patients with adrenocortical tumors, including in vitro investigation of BCL9...
February 8, 2018: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/29404451/microrna-therapy-inhibits-hepatoblastoma-growth-in-vivo-by-targeting-%C3%AE-catenin-and-wnt-signaling
#5
Emilie Indersie, Sarah Lesjean, Katarzyna B Hooks, Francis Sagliocco, Tony Ernault, Stefano Cairo, Maria Merched-Sauvage, Anne Rullier, Brigitte Le Bail, Sophie Taque, Michael Grotzer, Sophie Branchereau, Catherine Guettier, Monique Fabre, Laurence Brugières, Martin Hagedorn, Marie-Annick Buendia, Christophe F Grosset
Hepatoblastoma (HBL) is the most common pediatric liver cancer. In this malignant neoplasm, beta-catenin protein accumulates and increases Wnt signaling due to recurrent activating mutations in the catenin-beta 1 (CTNNB1) gene. Therefore, beta-catenin is a key therapeutic target in HBL. However, controlling beta-catenin production with therapeutic molecules has been challenging. New biological studies could provide alternative therapeutic solutions for the treatment of HBL, especially for advanced tumors and metastatic disease...
April 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29401606/cysteine-rich-protein-61-regulates-adipocyte-differentiation-from-mesenchymal-stem-cells-through-mammalian-target-of-rapamycin-complex-1-and-canonical-wnt-signaling
#6
Yongxu Yang, Qi Qi, Yi Wang, Yaru Shi, Weili Yang, Yunzhu Cen, Endong Zhu, Xiaoxia Li, Di Chen, Baoli Wang
Emerging evidence suggests that cysteine-rich protein 61 (CYR61) plays a role in the differentiation and development of chondrocytes, osteoblasts, and osteoclasts; however, little is known about its role in adipogenesis. The current study indicates that the expression level of Cyr61 was altered in primary cultured marrow stromal cells and the established mesenchymal cell line, C3H10T1/2, after adipogenic treatment. Overexpressing Cyr61 repressed C3H10T1/2 and primary marrow stromal cells to differentiate into mature adipocytes...
January 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29396901/fine-tuning-of-canonical-wnt-stimulation-enhances-differentiation-of-pluripotent-stem-cells-independent-of-%C3%AE-catenin-mediated-t-cell-factor-signaling
#7
Joseph Chen, Christian M Nefzger, Fernando J Rossello, Yu B Y Sun, Sue Mei Lim, Xiaodong Liu, Suzan de Boer, Anja S Knaupp, Jinhua Li, Kathryn C Davidson, Jose M Polo, Tiziano Barberi
The canonical Wnt/β-catenin pathway is crucial for early embryonic patterning, tissue homeostasis, and regeneration. While canonical Wnt/β-catenin stimulation has been used extensively to modulate pluripotency and differentiation of pluripotent stem cells (PSCs), the mechanism of these two seemingly opposing roles has not been fully characterized and is currently largely attributed to activation of nuclear Wnt target genes. Here, we show that low levels of Wnt stimulation via ectopic expression of Wnt1 or administration of glycogen synthase kinase-3 inhibitor CHIR99021 significantly increases PSC differentiation into neurons, cardiomyocytes and early endodermal intermediates...
February 2, 2018: Stem Cells
https://www.readbyqxmd.com/read/29363326/wnt-signaling-is-required-for-peritoneal-membrane-angiogenesis
#8
Manreet Kaur Padwal, Genyang Cheng, Limin Liu, Felix J Boivin, Azim Gangji, Kenneth Scott Brimble, Darren Bridgewater, Peter J Margetts
The WNT signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor beta (TGFB) mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis...
January 24, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29358554/knockdown-of-cripto-1-inhibits-the-proliferation-migration-invasion-and-angiogenesis-in-prostate-carcinoma-cells
#9
Ding Wu, Zhan Shi, Hao Xu, Renfu Chen, Song Xue, Xiaoqing Sun
Cripto-1 (CR-1) is a member of the epidermal growth factor-Cripto-1/FRL1/Cryptic gene family that plays a key role in the various malignant cancers. However, the role of CR-1 in prostate carcinoma (PCa) remains limited. The expression of CR-1 was down-regulated by small interfering RNA (siRNA). Western blot measured the expression levels of CR-1 and some related proteins. We performed Cell Counting Kit-8, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay and flow cytometry to detect the cellular proliferation and cycle...
September 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/29350052/protective-mechanisms-of-6-gingerol-in-dextran-sulfate-sodium-induced-chronic-ulcerative-colitis-in-mice
#10
B O Ajayi, I A Adedara, E O Farombi
Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive constituent of Zingiber officinale, which has been reported to possess various biological activities. This study was designed to evaluate the role of 6G in chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5% DSS followed by 14 days of normal drinking water...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29290587/rapgef5-regulates-nuclear-translocation-of-%C3%AE-catenin
#11
John N Griffin, Florencia Del Viso, Anna R Duncan, Andrew Robson, Woong Hwang, Saurabh Kulkarni, Karen J Liu, Mustafa K Khokha
Canonical Wnt signaling coordinates many critical aspects of embryonic development, while dysregulated Wnt signaling contributes to common diseases, including congenital malformations and cancer. The nuclear localization of β-catenin is the defining step in pathway activation. However, despite intensive investigation, the mechanisms regulating β-catenin nuclear transport remain undefined. In a patient with congenital heart disease and heterotaxy, a disorder of left-right patterning, we previously identified the guanine nucleotide exchange factor, RAPGEF5...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29276937/pirfenidone-inhibits-proliferation-and-promotes-apoptosis-of-hepatocellular-carcinoma-cells-by-inhibiting-the-wnt-%C3%AE-catenin-signaling-pathway
#12
Wei-Jie Zou, Zhi Huang, Tian-Peng Jiang, Ya-Ping Shen, An-Su Zhao, Shi Zhou, Shuai Zhang
BACKGROUND Hepatocellular carcinoma (HCC) is the most important cause of cancer-related deaths worldwide. Pirfenidone is an orally available small molecule with therapeutic potential for fibrotic diseases. MATERIAL AND METHODS In this study, we analyzed the effects of different pirfenidone concentrations on the proliferation of HepG2 HCC cells using Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was performed to measure the apoptotic effects of pirfenidone on HepG2 cells. Western blot analysis was performed to detect the expression of β-catenin and p-β-catenin...
December 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29275936/downregulation-of-akt2-attenuates-er-stress-induced-cytotoxicity-through-jnk-wnt-pathway-in-cardiomyocytes
#13
Yan-Xia Gao, Wen-Ting He, Long-Fei Pan, Hui Feng, Jiang-Li Sun, Bin Zhang, Lei Yu, Li-Jun Li
Akt, also known as protein kinase B (PKB), is a serine/threonine kinase that promotes survival and growth in response to extracellular signals. Akt1 has been demonstrated to play vital roles in cardiovascular diseases, but the role of Akt2 in cardiomyocytes is not fully understood. This study investigated the effect of Akt2 knockdown on tunicamycin (TM)-induced cytotoxicity in cardiomyocytes and the underlying mechanisms with a focus on the JNK-Wnt pathway. TM treatment significantly increased the expression of Akt2 at both mRNA and protein levels, which was shown to be mediated by the induction of reactive oxygen species (ROS)...
December 14, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29250807/the-wnt-transcriptional-switch-tle-removal-or-inactivation
#14
REVIEW
Aravinda-Bharathi Ramakrishnan, Abhishek Sinha, Vinson B Fan, Ken M Cadigan
Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a "transcriptional switch," repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood...
December 18, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29228681/cyclophosphamide-causes-osteoporosis-in-c57bl-6-male-mice-suppressive-effects-of-cyclophosphamide-on-osteoblastogenesis-and-osteoclastogenesis
#15
Dongfeng Zhao, Chenglong Wang, Yongjian Zhao, Bing Shu, Youji Jia, Shufen Liu, Hongshen Wang, Junli Chang, Weiwei Dai, Sheng Lu, Qi Shi, Yanping Yang, Yan Zhang, Yongjun Wang
The clinical evidence indicated that cyclophosphamide (CPD), one of the chemotherapy drugs, caused severe deteriorations in bones of cancer patients. However, the exact mechanisms by which CPD exerts effects on bone remodeling is not yet fully elucidated. Therefore, this study was performed to investigate the role and potential mechanism of CPD in osteoblastogenesis and osteoclastogenesis. Here it was found that CPD treatment (100mg/kg/day) for 7 days led to osteoporosis phenotype in male mice. CPD inhibited osteoblastogenesis as shown by decreasing the number and differentiation of bone mesenchymal stem cells (MSCs) and reducing the formation and activity of osteoblasts...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212806/syndecan-1-promotes-wnt-%C3%AE-catenin-signaling-in-multiple-myeloma-by-presenting-wnts-and-r-spondins
#16
Zemin Ren, Harmen van Andel, Wim de Lau, Robin B Hartholt, Madelon M Maurice, Hans Clevers, Marie José Kersten, Marcel Spaargaren, Steven T Pals
Multiple myeloma (MM) is characterized by the expansion of malignant plasma cells in the bone marrow (BM). Most MMs display aberrant Wnt/β-catenin signaling, which drives proliferation; however, they lack oncogenic Wnt-pathway mutations, suggesting activation by autocrine Wnt ligands and/or paracrine Wnts from the BM microenvironment. Expression of the heparan sulfate proteoglycan (HSPG) syndecan-1 is a hallmark of MM. Syndecan-1 is a critical player in the complex reciprocal interaction between MM cells and their BM niche, mediating growth factor/cytokine binding and signaling by its heparan sulfate (HS) chains...
December 6, 2017: Blood
https://www.readbyqxmd.com/read/29207102/lncrna-tug1-serves-an-important-role-in-hypoxia-induced-myocardial-cell-injury-by-regulating-the-mir%C3%A2-145%C3%A2-5p%C3%A2-binp3-axis
#17
Zhongwei Wu, Shengji Zhao, Chunfu Li, Chaoquan Liu
The aim of the present study was to investigate the function of long non‑coding RNA TUG1 in hypoxia‑induced myocardial cell injury and to explore the potential molecular mechanisms. The cardiomyocyte cell line H9c2 was cultured under hypoxic and normoxic conditions. TUG1 expression under hypoxic conditions was then detected. The effects of TUG1 overexpression on viability, apoptosis, migration and invasion were assayed. In addition, the microRNA (miR)‑145‑5p expression was detected. Following H9c2 cell transfection with miR‑145‑5p mimics, the H9c2 cell viability, apoptosis, migration and invasion were also detected...
November 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29207039/effective-component-of-salvia%C3%A2-miltiorrhiza-in-promoting-cardiomyogenic-differentiation-of-human-placenta%C3%A2-derived-mesenchymal-stem-cells
#18
Kun Li, Jieqiong Song, Qian Zhao, Bo Wang, Yunli Zhang, Xuezhe Wang, Tiantian Tang, Shizheng Li
Our previous study indicated that Salvia miltiorrhiza (SM) induced human placenta‑derived mesenchymal stem cells (hPDMSCs) to differentiate into cardiomyocytes, however, the effective component of SM in promoting cardiomyogenic differentiation remained to be elucidated. In the present study, the most commonly examined components of SM, including danshensu, salvianolic acid B, protocatechuic aldehyde, tanshinone I (TS I), TS IIA and cryptotanshinone, were used to determine the effective components of SM in promoting cardiomyogenic differentiation...
November 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29201214/sirt1-regulates-apoptosis-and-extracellular-matrix-degradation-in-resveratrol-treated-osteoarthritis-chondrocytes-via-the-wnt-%C3%AE-catenin-signaling-pathways
#19
Shuan Liu, Hongping Yang, Bing Hu, Mingyong Zhang
Osteoarthritis (OA) has become a major public health problem with the increased aging population. Previous studies have demonstrated that resveratrol (RES) was able to increase the level of sirtuin 1 (Sirt1) in OA chondrocytes. However, further investigations are required to elucidate the precise molecular mechanism of RES and the potential link between Sirt1 and RES. Therefore, the present study used 30 clinical OA chondrocyte to examine chondrocyte viability, apoptosis rate and the mRNA and protein expression levels of Sirt1 and relevant genes implicated in apoptosis, extracellular matrix (ECM) degradation and Wnt/β-catenin signaling pathway...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29175155/neuroanatomical-distribution-of-dek-protein-in-corticolimbic-circuits-associated-with-learning-and-memory-in-adult-male-and-female-mice
#20
Valentina Ghisays, Elizabeth T Nguyen, Joshua Streicher, Nicholas A Pease, Maureen Fitzgerald, Christina M Estrada, Ana Franco-Villanueva, Lisa Privette Vinnedge, Matia B Solomon
DEK, a chromatin-remodeling gene expressed in most human tissues, is known for its role in cancer biology and autoimmune diseases. DEK depletion in vitro reduces cellular proliferation, induces DNA damage subsequently leading to apoptosis, and down-regulates canonical Wnt/β-catenin signaling, a molecular pathway essential for learning and memory. Despite a recognized role in cancer (non-neuronal) cells, DEK expression and function is not well characterized in the central nervous system. We conducted a gene ontology analysis (ToppGene), using a cancer database to identify genes associated with DEK deficiency, which pinpointed several genes associated with cognitive-related diseases (i...
November 23, 2017: Neuroscience
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