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Dickkopf AND Wnt

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https://www.readbyqxmd.com/read/27864382/molecular-dynamics-of-dkk4-modulates-wnt-action-and-regulates-meibomian-gland-development
#1
Jian Sima, Yulan Piao, Yaohui Chen, David Schlessinger
Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, similar to that observed in Eda-ablated Tabby mice...
November 18, 2016: Development
https://www.readbyqxmd.com/read/27835606/neurokinin-1-receptor-is-a-novel-positive-regulator-of-wnt-%C3%AE-catenin-signaling-in-melanogenesis
#2
Jia Zhou, Jingjing Ling, Huizhu Song, Bei Lv, Lei Wang, Jing Shang, Yong Wang, Chunyan Chang, Fengfeng Ping, Jun Qian
Wnt/β-catenin signaling is essential for melanogenesis in melanocytes. Neurokinin-1 receptor (NK-1R) has recently been demonstrated to be involved in melanin production. However, the cross talk between NK-1R and Wnt/β-catenin is poorly understood. Here, [Sar9, Met(O2)11] substance P (SMSP) was used to activate NK-1R, while L-733060 was used to inhibit it. The effects of NK-1R activation and inhibition on Wnt and its inhibitors were analyzed using western blot and real-time quantitative PCR. The results showed that SMSP positively regulated Wnt/β-catenin signaling by increasing the expression of β-catenin and p-GSK3β protein, which resulted from the weakened expression of the Wnt inhibitor Dickkopf-1 (DKK1)...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832985/effects-of-raloxifene-against-letrozole-induced-bone-loss-in-chemically-induced-model-of-menopause-in-mice
#3
Abul Kalam, Sushama Talegaonkar, Divya Vohora
INTRODUCTION: The deleterious effects of letrozole, an aromatase inhibitor, used in the adjuvant treatment of breast cancer in postmenopausal women, on bone are well-documented and represent a major drawback to its clinical use. Raloxifene, a selective estrogen receptor modulator and a clinically approved anti-osteoporotic drug, has been recently demonstrated to be efficacious in women with breast cancer. The present study evaluated the effects of preventive and curative treatment with raloxifene on letrozole-induced alterations of bone microarchitecture and turnover markers in a chemically-induced menopause model in mice...
November 8, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27827955/a-novel-role-of-dickkopf-related-protein-3-in-macropinocytosis-in-human-bladder-cancer-t24-cells
#4
Nonoka Tsujimura, Nami O Yamada, Yuki Kuranaga, Minami Kumazaki, Haruka Shinohara, Kohei Taniguchi, Yukihiro Akao
Dickkopf-related protein 3 (Dkk-3) is a potential tumor suppressor reported in various cancer entities. However, we found that Dkk-3 was exceptionally upregulated in bladder cancer T24 cells. To validate the biological role of Dkk-3 other than a tumor suppressor, we examined the function of Dkk-3 in T24 cells. Gene silencing of Dkk-3 inhibited cell growth through inducing G₀/G₁ cell-cycle arrest. Furthermore, Dkk-3 knock-down caused macropinocytosis accompanied by autophagy, which were canceled in part by their inhibitors 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methyladenine (3-MA)...
November 5, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27807401/alzheimer-disease-crosstalk-between-the-canonical-wnt-beta-catenin-pathway-and-ppars-alpha-and-gamma
#5
REVIEW
Alexandre Vallée, Yves Lecarpentier
The molecular mechanisms underlying the pathophysiology of Alzheimer's disease (AD) are still not fully understood. In AD, Wnt/beta-catenin signaling has been shown to be downregulated while the peroxisome proliferator-activated receptor (PPAR) gamma (mARN and protein) is upregulated. Certain neurodegenerative diseases share the same Wnt/beta-catenin/PPAR gamma profile, such as bipolar disorder and schizophrenia. Conversely, other NDs share an opposite profile, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, multiple sclerosis, and Friedreich's ataxia...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27803037/opposing-roles-of-wnt-inhibitors-igfbp-4-and-dkk1-in-cardiac-ischemia-by-differential-targeting-of-lrp5-6-and-%C3%AE-catenin
#6
Da Wo, Jinhui Peng, Dan-Ni Ren, Liman Qiu, Jinxiao Chen, Ye Zhu, Yingjing Yan, Hongwei Yan, Jian Wu, En Ma, Tao Zhong, Yi-Han Chen, Zhong-Min Liu, Shangfeng Liu, Luoquan Ao, Zhenping Liu, Cizhong Jiang, Jun Peng, Yunzeng Zou, Qirong Qian, Weidong Zhu
BACKGROUND: -Myocardial infarction (MI) is one of the leading causes of morbidity and mortality worldwide, triggering irreversible myocardial cell damage and heart failure. The role of low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) as coreceptors of the Wnt/β-catenin pathway in the adult heart remain unknown. Insulin-like growth factor binding protein 4 (IGFBP-4) and dickkopf-related protein 1 (Dkk1) are two secreted LRP5/6 binding proteins which play a crucial role in heart development through preventing Wnt/β-catenin pathway activation...
November 1, 2016: Circulation
https://www.readbyqxmd.com/read/27801786/upregulated-microrna-25-mediates-the-migration-of-melanoma-cells-by-targeting-dkk3-through-the-wnt-%C3%AE-catenin-pathway
#7
Jia Huo, Yanfei Zhang, Ruilian Li, Yuan Wang, Jiawen Wu, Dingwei Zhang
Previous research indicates that microRNA-25 (miR-25) regulates carcinogenesis and the progression of various cancers, but the role of miR-25 in melanoma remains unclear. We observed that miR-25 was significantly upregulated in melanoma cell lines and tissue samples. Downregulation of miR-25 markedly suppressed invasion and proliferation of melanoma cells in vitro; however, overexpression of miR-25 markedly increased melanoma cell invasion and proliferation. Moreover, we observed Dickkopf-related protein 3 (DKK3) as a direct target of miR-25 in vitro...
October 27, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27774940/-wnt-%C3%AE-catenin-pathway-involved-in-the-regulation-of-rat-mesangial-cell-proliferation-by-adipose-derived-mesenchymal-stem-cells
#8
Zhi Li, Mengying Zhang, Xueqin Li, Jinming Lu, Liang Xu
Objective To investigate the effect of adipose-derived mesenchymal stem cells (ADSCs) on glomerular mesangial cell proliferation via Wnt/β-catenin pathway. Methods The rat glomerular mesangial cells (HBZY-1) were incubated in conditioned ADSC medium. Cell cycle was analyzed with flow cytometry; the proliferation rate of HBZY-1 and the expression levels of relative genes and proteins of Wnt signaling pathway were measured using RNA interference, quantitative real-time PCR and Western blotting, respectively...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27766367/increased-levels-of-dickkopf-1-are-indicative-of-wnt-%C3%AE-catenin-downregulation-and-lower-osteoblast-signaling-in-children-and-adolescents-with-type-1-diabetes-mellitus-contributing-to-lower-bone-mineral-density
#9
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
https://www.readbyqxmd.com/read/27733096/endogenous-dkk1-and-frzb-regulate-chondrogenesis-and-hypertrophy-in-three-dimensional-cultures-of-human-chondrocytes-and-human-mesenchymal-stem-cells
#10
Leilei Zhong, Xiaobin Huang, Emilie Dooms Rodrigues, Jeroen C H Leijten, Theo Verrips, Mohamed El Khattabi, Marcel Karperien, Janine N Post
Hypertrophic differentiation occurs during in vitro chondrogenesis of mesenchymal stem cells (MSCs), decreasing the quality of the cartilage construct. Previously we identified WNT pathway antagonists Dickkopf 1 homolog (DKK1) and frizzled-related protein (FRZB) as key factors in blocking hypertrophic differentiation of human MSCs (hMSCs). In this study, we investigated the role of endogenously expressed DKK1 and FRZB in chondrogenesis of hMSC and chondrocyte redifferentiation and in preventing cell hypertrophy using three relevant human cell based systems, isolated hMSCs, isolated primary human chondrocytes (hChs), and cocultures of hMSCs with hChs for which we specifically designed neutralizing nano-antibodies...
December 1, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27732331/high-sclerostin-and-dickkopf-1-dkk-1-serum-levels-in-children-and-adolescents-with-type-1-diabetes-mellitus
#11
Maria Felicia Faienza, Annamaria Ventura, Maurizio Delvecchio, Anna Fusillo, Laura Piacente, Gabriella Aceto, Graziana Colaianni, Silvia Colucci, Luciano Cavallo, Maria Grano, Giacomina Brunetti
CONTEXT: Childhood type 1 diabetes (T1DM) is associated with decreased bone mass. Sclerostin and dickkopf-1 (DKK-1) are Wnt inhibitors which regulate bone formation. OBJECTIVE: To evaluate sclerostin and DKK-1 levels in TD1M children and to analyze the influence of the glycaemic control on bone health. DESIGN AND SETTING: Cross-sectional study conducted at a clinical research center. Partecipants: One hundred and six T1DM subjects (12.2 ± 4 years), 66 on multiple daily injections (MDI) and 40 on continuous subcutaneous infusion of insulin (CSII), and 80 controls...
October 12, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27699213/tubular-dickkopf-3-promotes-the-development-of-renal-atrophy-and-fibrosis
#12
Giuseppina Federico, Michael Meister, Daniel Mathow, Gunnar H Heine, Gerhard Moldenhauer, Zoran V Popovic, Viola Nordström, Annette Kopp-Schneider, Thomas Hielscher, Peter J Nelson, Franz Schaefer, Stefan Porubsky, Danilo Fliser, Bernd Arnold, Hermann-Josef Gröne
Renal tubular atrophy and interstitial fibrosis are common hallmarks of etiologically different progressive chronic kidney diseases (CKD) that eventually result in organ failure. Even though these pathological manifestations constitute a major public health problem, diagnostic tests, as well as therapeutic options, are currently limited. Members of the dickkopf (DKK) family, DKK1 and -2, have been associated with inhibition of Wnt signaling and organ fibrosis. Here, we identify DKK3 as a stress-induced, tubular epithelia-derived, secreted glycoprotein that mediates kidney fibrosis...
January 21, 2016: JCI Insight
https://www.readbyqxmd.com/read/27670695/the-role-of-dickkopf-1-in-joint-remodeling-and-fibrosis-a-link-connecting-spondyloarthropathies-and-scleroderma
#13
Kalliopi Klavdianou, Stamatis-Nick Liossis, Lazaros Sakkas, Dimitrios Daoussis
BACKGROUND: Dickkopf-1 (Dkk-1) is a soluble inhibitor of the canonical Wnt pathway, which plays critical roles in embryonic development. Evidence suggests that this molecule regulates several aspects of both bone biology and fibrosis. OBJECTIVES: To provide an overview of our current knowledge of the role of Dkk-1 in joint remodeling and fibrosis. METHODS: We performed an electronic search (Medline) using the following key words: Dickkopf-1 (or Dkk-1), new bone formation, joint remodeling, ankylosing spondylitis, systemic sclerosis (or scleroderma), and fibrosis, supplemented by a manual search of references from retrieved articles...
August 23, 2016: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/27648363/cordycepin-promotes-apoptosis-by-modulating-the-erk-jnk-signaling-pathway-via-dusp5-in-renal-cancer-cells
#14
Jung-Hoo Hwang, Jong Cheon Joo, Dae Joon Kim, Eunbi Jo, Hwa-Seung Yoo, Kyung-Bok Lee, Soo Jung Park, Ik-Soon Jang
Constitutive activation of extracellular signal regulated kinase (ERK)-Jun NH2-terminal kinase (JNK) signaling commonly occurs in tumors. The activation of ERK promotes cell proliferation, whereas that of JNK induces cell apoptosis. However, the apoptotic mechanism of ERK-JNK signaling in cancer is not well understood. Recently, we identified that apoptosis and activation of the JNK signaling pathway were induced after cordycepin treatment in human renal cancer, suggesting that JNK signaling might contribute to TK-10 cell apoptosis...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27610015/therapeutic-potential-of-targeting-acinar-cell-reprogramming-in-pancreatic-cancer
#15
REVIEW
Chi-Hin Wong, You-Jia Li, Yang-Chao Chen
Pancreatic ductal adenocarcinoma (PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRas(G12D) mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinar-to-ductal-metaplasia (ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia (PanIN) and eventually PDAC...
August 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27593374/reversal-of-synapse-degeneration-by-restoring-wnt-signaling-in-the-adult-hippocampus
#16
Aude Marzo, Soledad Galli, Douglas Lopes, Faye McLeod, Marina Podpolny, Margarita Segovia-Roldan, Lorenza Ciani, Silvia Purro, Francesca Cacucci, Alasdair Gibb, Patricia C Salinas
Synapse degeneration occurs early in neurodegenerative diseases and correlates strongly with cognitive decline in Alzheimer's disease (AD). The molecular mechanisms that trigger synapse vulnerability and those that promote synapse regeneration after substantial synaptic failure remain poorly understood. Increasing evidence suggests a link between a deficiency in Wnt signaling and AD. The secreted Wnt antagonist Dickkopf-1 (Dkk1), which is elevated in AD, contributes to amyloid-β-mediated synaptic failure. However, the impact of Dkk1 at the circuit level and the mechanism by which synapses disassemble have not yet been explored...
October 10, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27580425/differences-in-expression-of-wnt-antagonist-dkk1-in-healthy-versus-pathological-bone-samples
#17
S Ray, T El Khassawna, U Sommer, U Thormann, N D Wijekoon, K Lips, C Heiss, V Alt
Wnt/β-catenin signalling components was shown to affect bone cells function including chondrocytes.Secreted Dkk1, a potent osteogenesis inhibiting factor mediates bone loss in diseased bones by suppressing the biological actions of Wnt proteins. In addition, increased Dkk1 signalling inhibits chondrogenesis in new bone formation. Recent findings also show there exists a cross-talk between the chondrocytes and the cells of the osteoblast lineage, which are the most affected cell types in muskuloskeletal disorders...
August 31, 2016: Journal of Microscopy
https://www.readbyqxmd.com/read/27578583/-tenascin-c-knockdown-suppresses-osteoblast-differentiation-and-promotes-osteoporosis-in-mice-by-inhibiting-wnt-signaling
#18
Yu Chen, Zi-Feng Chen, Fan He
OBJECTIVE: To understand the mechanism by which tenascin-C regulates osteoblast differentiation and the role of tenascin-C in osteoporosis. METHODS: Tenascin-C protein expression in femoral spongy bone of mice with or without osteoporosis was analyzed using Western blotting. In MC3T3-E1 osteoblasts with or without tenascin-C depletion by a specific siRNA targeting tenascin-C, alkaline phosphatase activity and Dickkopf-1 (DKK-1) expression were determined using quantitative RT-PCR and Western blotting, and the transcriptional activity of Wnt signaling pathway was analyzed using a luciferase reporter assay...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27573735/high-serum-levels-of-sclerostin-and-dickkopf-1-are-associated-with-acute-ischaemic-stroke
#19
Xin-Wei He, En Wang, Yu-Yan Bao, Feng Wang, Ming Zhu, Xiao-Fei Hu, Xiao-Ping Jin
BACKGROUND AND AIMS: Sclerostin and Dickkopf-1 (Dkk-1) are potent antagonists of Wnt signalling and might therefore play important roles in cardiovascular disease. We investigated whether serum sclerostin and Dkk-1 levels are associated with acute ischaemic stroke and specific stroke subtypes. METHODS: Serum levels of sclerostin and Dkk-1 were measured by ELISA on day 1 and on day 6 after stroke in 62 patients with large artery atherosclerotic (LAA) stroke, on day 1 after stroke in 62 age- and gender-matched patients with small-artery occlusion (SAO) stroke and on admission in 62 healthy controls...
October 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27571062/wnt-%C3%AE-catenin-signaling-mediated-uch-l1-expression-in-podocytes-of-diabetic-nephropathy
#20
Hongxia Zhang, Weili Luo, Yonghong Sun, Yanchun Qiao, Liying Zhang, Zhilian Zhao, Shijun Lv
Increasing studies identified podocyte injury as a key early risk factor resulting in diabetic nephropathy (DN). The ubiquitin carboxy-terminal hydrolase 1 (UCH-L1) participates in podocyte differentiation and injury, which is elevated in the podocytes of a variety of nephritis. Whether UCH-L1 expression is positively related to podocyte injury of DN remains unclear. In this study, elevated expression of UCH-L1 and its intrinsic mechanism in high glucose (HG)-stimulated murine podocytes were investigated using western blot and real-time quantitative PCR...
2016: International Journal of Molecular Sciences
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