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Dickkopf AND Wnt

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https://www.readbyqxmd.com/read/28749252/the-role-of-dickkopf-1-as-a-potential-prognostic-marker-in-pancreatic-ductal-adenocarcinoma
#1
De-Jun Liu, Yue-Xia Xie, Xiao-Xing Liu, Yan-Miao Huo, Min-Wei Yang, Xue-Liang Fu, Wei Liu, Jian-Yu Yang, Jiao Li, Rong Hua, Pei-Feng Liu, Yong-Wei Sun, Jun-Feng Zhang
Dickkopf-1(DKK-1), the downstream target of β-catenin/T-cell factor, participates in a negative feedback loop in the Wnt signaling and reported as an important biomarker in many tumors. In this study, we analyzed the expression of DKK-1 in pancreatic ductal adenocarcinoma (PDAC) patients at both mRNA and protein levels. We used real-time PCR to detect the expression of DKK-1 in 32 PDAC and paired adjacent non-tumor tissues, results suggested that the expression of DKK-1 was increased in PDAC tissues. We found the similar results in the analysis of three independent microarray datasets...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28744803/xanthoceraside-modulates-neurogenesis-to-ameliorate-cognitive-impairment-in-app-ps1-transgenic-mice
#2
Lin Zhu, Tianyan Chi, Xuemei Zhao, Lei Yang, Shijie Song, Qiaohui Lu, Xuefei Ji, Peng Liu, Lihua Wang, Libo Zou
Neuronal loss is reported to be an important pathological process in Alzheimer's disease (AD). Neurogenesis is a process of generation of new neurons to fill the neuronal loss. Xanthoceraside has been shown to attenuate the cognitive deficits in several AD animal models. However, little is known about the effect of xanthoceraside on neurogenesis in APP/PS1 transgenic mice. Thus, in this study, we investigated whether xanthoceraside can ameliorate learning and memory impairment by promoting NSCs proliferation and neuronal differentiation...
July 25, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28738084/the-dkk3-gene-encodes-a-vital-intracellular-regulator-of-cell-proliferation
#3
Jack L Leonard, Deborah M Leonard, Scot A Wolfe, Jilin Liu, Jaime Rivera, Michelle Yang, Ryan T Leonard, Jacob P S Johnson, Prashant Kumar, Kate L Liebmann, Amanda A Tutto, Zhongming Mou, Karl J Simin
Members of the Dickkopf (Dkk) family of Wnt antagonists interrupt Wnt-induced receptor assembly and participate in axial patterning and cell fate determination. One family member, DKK3, does not block Wnt receptor activation. Loss of Dkk3 expression in cancer is associated with hyperproliferation and dysregulated ß-catenin signaling, and ectopic expression of Dkk3 halts cancer growth. The molecular events mediating the DKK3-dependent arrest of ß-catenin-driven cell proliferation in cancer cells are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#4
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28715139/uvb-exposure-of-a-humanized-skin-model-reveals-unexpected-dynamic-of-keratinocyte-proliferation-and-wnt-inhibitor-balancing
#5
Teresa Michalczyk, Thomas Biedermann, Sophie Böttcher-Haberzeth, Agnes S Klar, Martin Meuli, Ernst Reichmann
We developed human dermo-epidermal skin substitutes which are presently applied in phase I and II clinical trials. Here we used these very same skin equivalents containing melanocytes, named MelSkin, as an experimental skin model. We investigated the effects of UVB irradiation on the skin grafts transplanted on immune-compromised rats. The irradiation induces a strong wound healing response going along with massive proliferation of basal keratinocytes, basically quiescent under non-irradiated, homeostatic conditions...
July 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28710530/proteomic-characterisation-reveals-active-wnt-signalling-by-human-multipotent-stromal-cells-as-a-key-regulator-of-beta-cell-survival-and-proliferation
#6
Miljan Kuljanin, Gillian I Bell, Stephen E Sherman, Gilles A Lajoie, David A Hess
AIMS/HYPOTHESIS: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. METHODS: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSC(R)) vs nonregenerative (MSC(NR)) capacity...
July 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28692808/modulating-wnt-signaling-rescues-palate-morphogenesis-in-pax9-mutant-mice
#7
C Li, Y Lan, R Krumlauf, R Jiang
Cleft palate is a common birth defect caused by disruption of palatogenesis during embryonic development. Although mutations disrupting components of the Wnt signaling pathway have been associated with cleft lip and palate in humans and mice, the mechanisms involving canonical Wnt signaling and its regulation in secondary palate development are not well understood. Here, we report that canonical Wnt signaling plays an important role in Pax9-mediated regulation of secondary palate development. We found that cleft palate pathogenesis in Pax9-deficient embryos is accompanied by significantly reduced expression of Axin2, an endogenous target of canonical Wnt signaling, in the developing palatal mesenchyme, particularly in the posterior regions of the palatal shelves...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28686724/dipeptidyl-peptidase-4-inhibitor-gemigliptin-protects-against-vascular-calcification-in-an-experimental-chronic-kidney-disease-and-vascular-smooth-muscle-cells
#8
Soon-Youn Choi, Hye-Myung Ryu, Eun-Joo Oh, Ji-Young Choi, Jang-Hee Cho, Chan-Duck Kim, Yong-Lim Kim, Sun-Hee Park
Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats...
2017: PloS One
https://www.readbyqxmd.com/read/28685176/the-hormetic-functions-of-wnt-pathways-in-tubular-injury
#9
REVIEW
Elisabeth F Gröne, Giuseppina Federico, Peter J Nelson, Bernd Arnold, Hermann-Josef Gröne
Chronic tubulointerstitial damage with tubular epithelial atrophy and interstitial fibrosis is the hallmark of chronic kidney disease (CKD) and a predictor for progression of CKD.Several experiments have now provided evidence that the Wnt signaling pathways are significantly contributing to atrophy and fibrosis; in contrast, it also has been shown that the Wnt system fosters regenerative processes in acute tubular injury.We now have demonstrated that Dickkopf 3 (DKK3) is an agonist for canonical Wnt signaling in CKD and fosters chronic fibrosing inflammation of the tubulointerstitial compartment...
July 6, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28677426/dkk1-promotes-migration-and-invasion-of-non-small-cell-lung-cancer-via-%C3%AE-catenin-signaling-pathway
#10
Jing Zhang, Xintong Zhang, Xiaoting Zhao, Mei Jiang, Meng Gu, Ziyu Wang, Wentao Yue
Disregulation of dickkopf-related protein 1 (DKK1) has been reported in a variety of human cancers. However, how DKK1 functions in Non-small cell lung cancer has not been revealed. In the current study, DKK1 was knocked out by the lentivirus-mediated short hairpin RNA interference approach in H1299 and 95C non-small cell lung cancer cell lines. Subsequently, the migration and invasion ability were assessed by wound-healing and transwell assays. In addition, epithelial-mesenchymal transition markers and β-catenin were examined by Western blot analysis...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28676900/serum-levels-of-the-bone-turnover-markers-dickkopf-1-osteoprotegerin-and-tnf-%C3%AE-in-knee-osteoarthritis-patients
#11
Sicong Min, Chao Wang, Wanli Lu, Zhihong Xu, Dongquan Shi, Dongyang Chen, Huajian Teng, Qing Jiang
Knee osteoarthritis (KOA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Several inflammatory markers and cartilage degradation products can be used as biomarkers in OA. The key factors of bone metabolism in normal joint bone, dickkopf-1 (DKK1) and osteoprotegerin (OPG), interact with Wnt signaling pathway, balancing between bone absorption and bone reconstruction. TNF-α is a key inducer of DKK-1, which belongs to the family of proteins involved in joint remodeling...
July 4, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28659791/pentazocine-protects-sn4741-cells-against-mpp-induced-cell-damage-via-up-regulation-of-the-canonical-wnt-%C3%AE-catenin-signaling-pathway
#12
Jiancai Wang, Jintao Gu, Hao Wu, Gang Zhu, Dayun Feng, Yuqian Li, Wei Guo, Keyong Tian, Guodong Gao, Li Gao
The Wnt/β-catenin signaling pathway has been linked to many neurodegenerative diseases including Parkinson's disease (PD). A glycoprotein named Dickkopf-1 (Dkk1) can combine with the receptor complex on cell membrane to inhibit Wnt/β-catenin signaling. Opioids, a series of compounds including morphine, fentanyl and pentazocine, have been reported to contribute to the up-regulation of Wnt/β-catenin signaling. Naloxone is an antagonist that has been used as an antidote to opioids through mu-opioid receptor...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28652180/serum-levels-of-dickkopf-1-are-a-potential-negative-biomarker-of-survival-in-geriatric-patients
#13
Peter Dovjak, Georg Heinze, Anna Rainer, Wolfgang Sipos, Peter Pietschmann
Fragility fractures due to osteoporosis and its most dreaded complication - hip fractures - are the cause of disability, high mortality and place a considerable burden on global health economics. Although much work has been done to accurately predict mortality and find risk factors for poor health outcome, little attention was given to the Wnt-catenin signaling pathway and its role in the posttraumatic course of disease. We studied 238 geriatric patients (175 women (mean age 84yrs) and 63 men (mean age 82yrs)) in total that were admitted to a department of Acute Geriatric Care...
June 23, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28634697/in-psoriatic-arthritis-dkk-1-and-pth-are-lower-than-in-rheumatoid-arthritis-and-healthy-controls
#14
Angelo Fassio, Luca Idolazzi, Ombretta Viapiana, Camilla Benini, Elisabetta Vantaggiato, Francesco Bertoldo, Maurizio Rossini, Davide Gatti
Psoriatic Arthritis (PsA) is characterized by bone erosive damage often associated with exuberant bone formation especially in enthesial sites. Dkk-1 and sclerostin are the main inhibitors of the WNT/β-catenin signaling pathway and play a key role in the regulation of both bone formation and resorption. We performed this study in order to compare the serum levels of the WNT-pathway regulators along with bone turnover markers (BTM) and parathyroid hormone (PTH) between three different groups: one group of female patients affected by PsA, one group of female patients affected by rheumatoid arthritis (RA), and healthy female controls (HC)...
June 20, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28628652/microrna-433-3p-promotes-osteoblast-differentiation-through-targeting-dkk1-expression
#15
Xiaolin Tang, Jiantao Lin, Guanhai Wang, Jianlin Lu
Dickkopf-1 (DKK1) is a powerful antagonist of canonical WNT signaling pathway, and is regarded as a biomarker for osteoporosis. Its expression is highly correlated with bone mass and osteoblasts maturation. In this study, mouse primary bone marrow cells and osteoblast cell lines were used. Luciferase reporter assay and western blotting methods were employed to validate if miRNA-433-3p epigenetically regulated DKK1 translation. Rat bone marrow derived osteoblasts were infected with lentivirus vector in which miR-433-3p was constructed...
2017: PloS One
https://www.readbyqxmd.com/read/28627829/mir-29a-and-messenger-rna-expression-of-bone-turnover-markers-in-canonical-wnt-pathway-in-patients-with-ankylosing-spondylitis
#16
Jinxian Huang, Guoxiang Song, Zhihua Yin, Zhongchao Fu, Zhizhong Ye
BACKGROUND: Recent studies showed that the canonical Wnt pathway and miR-29a play important roles in the pathogenesis of bone formation. We studied the levels of miR-29a and messenger RNA (mRNA) of bone turnover markers in the canonical Wnt pathway in ankylosing spondylitis (AS). METHODS: The levels of miR-29a and mRNA of bone turnover markers in canonical Wnt pathway from peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction in 38 patients with AS and 32 healthy controls...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28607150/wnt3a-induces-the-expression-of-acetylcholinesterase-during-osteoblast-differentiation-via-the-runx2-transcription-factor
#17
Miranda L Xu, Cathy W C Bi, Etta Y L Liu, Tina T X Dong, Karl W K Tsim
Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic transmission in neurons. Apart from this AChE activity, emerging evidence suggests that AChE could also function in other, nonneuronal cells. For instance, in bone, AChE exists as a proline-rich membrane anchor (PRiMA)-linked globular form in osteoblasts, in which it is proposed to play a noncholinergic role in differentiation. However, this hypothesis is untested. Here, we found that in cultured rat osteoblasts, AChE expression was increased in parallel with osteoblastic differentiation...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28587752/dickkopf-1-inhibits-wnt3a-induced-migration-and-epithelial-mesenchymal-transition-of-human-lens-epithelial-cells
#18
Tingting Liu, Limin Zhang, Yanyan Wang, Haitao Zhang, Lin Li, Xiuli Bao
Posterior capsular opacification (PCO) is a major post-operative complication of cataract surgery. Epithelial-mesenchymal transition (EMT) contributes to PCO. We previously indicated that Wnt3a induces the EMT of human lens epithelial cells (LECs) and plays an important role in the development of PCO. The present study aimed to test the potential effect of Dickkopf-1 (Dkk1) on Wnt3a-induced cell migration and the EMT of LECs and to explore possible cellular mechanisms. The secretion of Dkk1 was reduced in the rabbit PCO model, and Dkk1 injected into the eyes post-surgical manipulation prevented PCO formation...
June 3, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28575156/consequences-of-endogenous-and-exogenous-wnt-signaling-for-development-in-the-preimplantation-bovine-embryo%C3%A2
#19
Paula Tribulo, Beatriz Caetano da Silva Leão, Khoboso C Lehloenya, Gisele Zoccal Mingoti, Peter J Hansen
Although WNT signaling regulates several developmental processes, its specific role during preimplantation development remains unclear. The present aim was to evaluate the consequences of activation and inhibition of β-catenin (CTNNB1) dependent and -independent WNT signaling in the bovine preimplantation embryo. Activation of CTNNB1 mediated WNT signaling by the agonist 2-amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) and a glycogen synthase kinase 3 (GSK3) inhibitor reduced development to the blastocyst stage...
May 30, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28574171/rationale-for-targeting-the-wnt-signaling-modulator-dkk1-for-oncology
#20
REVIEW
Michael H Kagey, Xi He
Wnt signaling is a fundamental pathway involved in embryonic development and adult tissue homeostasis. Mutations in the pathway frequently lead to developmental defects and cancer. As such, therapeutic intervention of this pathway has generated tremendous interest. Dickkopf-1 (DKK1) is a secreted inhibitor of β-catenin dependent Wnt signaling and was originally characterized as a tumor suppressor based on the prevailing view that Wnt signaling promotes cancer pathogenesis. However, DKK1 appears to increase tumor growth and metastasis in pre-clinical models and its elevated expression correlates with a poor prognosis in a range of cancers, indicating that DKK1 has more complex cellular and biological functions than originally appreciated...
June 2, 2017: British Journal of Pharmacology
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