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https://www.readbyqxmd.com/read/29128669/wip1-regulates-blood-brain-barrier-function-and-neuro-inflammation-induced-by-lipopolysaccharide-via-the-sonic-hedgehog-signaling-signaling-pathway
#1
Hong Zhen, Lize Zhao, Zhangjun Ling, Li Kuo, Xiarui Xue, Jiaxiu Feng
The blood brain barrier (BBB) is a diffusion barrier that maintains the brain environment. Wip1 is a nuclear phosphatase induced by many factors and involved in various stresses, tumorigenesis, organismal aging, and neurogenesis. Wip1's role in BBB integrity has not been thoroughly investigated. The purpose of the present study was to investigate the effect and mechanism of Wip1 on lipopolysaccharide (LPS)-induced BBB dysfunction and inflammation in an in vitro BBB model. The in vitro BBB model was established by co-culturing human brain-microvascular endothelial cells and human astrocytes and then exposing them to 1μg/ml LPS for 6, 12, 18, 24, and 48h...
November 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29039507/effect-of-the-adenovirus%C3%A2-mediated-wip1-gene-on-lumbar-intervertebral-disc-degeneration-in-a-rabbit-model
#2
Yuan Wang, Yong Yang, Jing-Chuan Sun, Qin-Jie Kong, Hai-Bo Wang, Jian-Gang Shi
The present study aimed to investigate the effect of the adenovirus‑mediated wild‑type p53‑induced protein phosphatase 1 (Wip1) gene on lumbar disc degeneration (LDD) in a rabbit model. Adult New Zealand white rabbits were used as experimental subjects. The rabbits were divided into LDD groups (groups A‑C of rabbit models of LDD) and control groups (groups D‑F of normal rabbits). The animals in groups A and D were injected with the Wip1 gene vector, those in groups B and E were injected with an empty vector, and those in groups C and F were injected with phosphate‑buffered saline...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28968438/microrna-16-feedback-loop-with-p53-and-wip1-can-regulate-cell-fate-determination-between-apoptosis-and-senescence-in-dna-damage-response
#3
Maria Vitória C Issler, José Carlos M Mombach
Cell fate regulation is an open problem whose comprehension impacts several areas of the biosciences. DNA damage induces cell cycle checkpoints that activate the p53 pathway to regulate cell fate mechanisms such as apoptosis or senescence. Experiments with different cell types show that the p53 pathway regulates cell fate through a switch behavior in its dynamics. For low DNA damage the pathway presents an oscillatory pattern associated with intense DNA damage repair while for high damage there are no oscillations and either p53 concentration increases inducing apoptosis or the cell enters a senescence state...
2017: PloS One
https://www.readbyqxmd.com/read/28959360/role-of-wild-type-p53-induced-phosphatase-1-in-cancer
#4
Zhi-Peng Wang, Ye Tian, Jun Lin
Wild-type p53-induced phosphatase (Wip1) is a member of the protein phosphatase type 2C family and is an established oncogene due to its dephosphorylation of several tumor suppressors and negative control of the DNA damage response system. It has been reported to dephosphorylate p53, ataxia telangiectasia mutated, checkpoint kinase 1 and p38 mitogen activated protein kinases, forming negative feedback loops to inhibit apoptosis and cell cycle arrest. Wip1 serves a major role in tumorigenesis, progression, invasion, distant metastasis and apoptosis in various types of human cancer...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28915621/wip1-is-associated-with-tumorigenity-and-metastasis-through-mmp-2-in-human-intrahepatic-cholangiocarcinoma
#5
Sulai Liu, Bo Jiang, Hao Li, Zili He, Pin Lv, Chuang Peng, Yonggang Wang, Wei Cheng, Zhengquan Xu, Wei Chen, Zhengkai Liu, Bao Zhang, Shengqian Shen, Shuanglin Xiang
Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903382/microrna16-regulates-glioma-cell-proliferation-apoptosis-and-invasion-by-targeting-wip1-atm-p53-feedback-loop
#6
Xiao-Hong Zhan, Qiu-Yan Xu, Rui Tian, Hong Yan, Min Zhang, Jing Wu, Wei Wang, Jie He
The present study aimed to investigate the role and underlying mechanisms of microRNA16 (miR-16) on proliferation, apoptosis and invasion of glioma cells. The cell models of miR-16 upregulation and Negative control group (NC group) were built. The cell functions of different groups were detected by colony formation assay, transwell chamber assay, proliferation, apoptosis and cycle experiments. The intracranial orthotopic transplantation animal models were built to different groups: miR-16 agomir group, miR-16 antagomir group and their NC group...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878779/wip1-deficiency-promotes-neutrophil-recruitment-to-the-infection-site-and-improves-sepsis-outcome
#7
Xiao-Fei Shen, Yang Zhao, Ke Cao, Wen-Xian Guan, Xue Li, Qian Zhang, Yong Zhao, Yi-Tao Ding, Jun-Feng Du
Sepsis is defined as an uncontrolled host response to infection, and no specific therapy or drugs have been used in clinical trials currently. Discovering new therapeutic targets for sepsis treatment has always been a central problem in the field of sepsis research. Neutrophils stand at the first line in controlling infection and have been identified to be dysregulated with impaired migration and antimicrobial function during sepsis. Based on our previous results on demonstrating wild-type p53-induced phosphatase 1 in controlling neutrophil development, we explored the possible relationship among Wip1, neutrophils, and sepsis in the present study...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28822916/wip1-dependent-modulation-of-macrophage-migration-and-phagocytosis
#8
Yiting Tang, Bing Pan, Xin Zhou, Kai Xiong, Qian Gao, Lei Huang, Ying Xia, Ming Shen, Shulin Yang, Honglin Liu, Tao Tan, Jianjie Ma, Xuehong Xu, Yulian Mu, Kui Li
Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. Controlling macrophage conversion into foam cells remains a major challenge for treatment of atherosclerotic diseases. Here, we show that Wip1, a member of the PP2C family of Ser/Thr protein phosphatases, modulates macrophage migration and phagocytosis associated with atherosclerotic plaque formation. Wip1 deficiency increases migratory and phagocytic activities of the macrophage under stress conditions. Enhanced migration of Wip1(-/-) macrophages is mediated by Rac1-GTPase and PI3K/AKT signalling pathways...
August 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28780681/interaction-of-wip1-and-nf-%C3%AE%C2%BAb-regulates-neuroinflammatory-response-in-astrocytes
#9
Fan Xu, Lifei Chen, Xin Zhao, Haibin Zhong, Ling Cui, Li Jiang, Hui Huang, Li Li, Siming Zeng, Min Li
OBJECTIVE: The aims of the present study were to detect the interaction of Wip1 and NF-κB P65 in retina of an LPS-induced astrocytes activation model. METHODS: The interaction between Wip1 and nuclear factor kappa B (NF-κB) P65 was observed in lipopolysaccharide (LPS)-stimulated primary rat astrocytes derived from retina. The expressions of Wip1 and NF-κB P65 were evaluated using Western blot and RT-PCR. Small interfering RNA (siRNA) against Wip1 was transfected into astrocytes to clarify the phosphorylation status and nuclear translocation of NF-κB P65 and expressions of these proinflammatory factors...
November 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28732646/phosphatase-wip1-controls-the-development-of-th9-cells-and-allergic-airway-inflammation
#10
Peng Wang, Huiting Su, Lianjun Zhang, Hui Chen, Xuelian Hu, Fan Yang, Jun Lu, Lianfeng Zhang, Yong Zhao
BACKGROUND: Allergic asthma is one of the most common diseases worldwide, resulting in a burden of diseases. No available therapeutic regimens can cure asthma so far. OBJECTIVE: To identify new molecular targets for Th9 cells-mediated allergic airway inflammation. METHODS: Wild-type p53-induced phosphatase 1 (Wip1) gene knockout mice, Wip1 inhibitor-treated mice and ovalbumin (OVA)-induced allergic airway inflammation mouse models were employed to characterize the roles of Wip1 in allergic airway inflammation...
July 18, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28654910/microrna16-regulates-glioma-cell-proliferation-apoptosis-and-invasion-by-targeting-wip1-atm-p53-feedback-loop
#11
Xiao-Hong Zhan, Qiu-Yan Xu, Rui Tian, Hong Yan, Min Zhang, Jing Wu, Wei Wang, Jie He
The present study aimed to investigate the role and underlying mechanisms of microRNA16 (miR-16) on proliferation, apoptosis and invasion of glioma cells. The cell models of miR-16 upregulation and Negative control group (NC group) were built. The cell functions of different groups were detected by colony formation assay, transwell chamber assay, proliferation, apoptosis and cycle experiments. The intracranial orthotopic transplantation animal models were built to different groups: miR-16 agomir group, miR-16 antagomir group and their NC group...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28607002/atm-wip1-activities-at-chromatin-control-plk1-re-activation-to-determine-g2-checkpoint-duration
#12
Himjyot Jaiswal, Jan Benada, Erik Müllers, Karen Akopyan, Kamila Burdova, Tobias Koolmeister, Thomas Helleday, René H Medema, Libor Macurek, Arne Lindqvist
After DNA damage, the cell cycle is arrested to avoid propagation of mutations. Arrest in G2 phase is initiated by ATM-/ATR-dependent signaling that inhibits mitosis-promoting kinases such as Plk1. At the same time, Plk1 can counteract ATR-dependent signaling and is required for eventual resumption of the cell cycle. However, what determines when Plk1 activity can resume remains unclear. Here, we use FRET-based reporters to show that a global spread of ATM activity on chromatin and phosphorylation of ATM targets including KAP1 control Plk1 re-activation...
July 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28599292/wip1-is-associated-with-tumorigenity-and-metastasis-through-mmp-2-in-human-intrahepatic-cholangiocarcinoma
#13
Sulai Liu, Bo Jiang, Hao Li, Zili He, Pin Lv, Chuang Peng, Yonggang Wang, Wei Cheng, Zhengquan Xu, Wei Chen, Zhengkai Liu, Bao Zhang, Shengqian Shen, Shuanglin Xiang
Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524834/wild-type-p53-induced-phosphatase-1-deficiency-exacerbates-myocardial-infarction-induced-ischemic-injury
#14
Ke-Mei Liu, Hai-Hong Zhang, Ya-Nan Wang, Lian-Mei Wang, Hong-Yu Chen, Cai-Feng Long, Lian-Feng Zhang, Hong-Bing Zhang, Hong-Bing Yan
BACKGROUND: Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wip1) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wip1 in cardiac adaptation to MI is unknown. We investigated the significance of Wip1 in a mouse model of MI. METHODS: The study began in June 2014 and was completed in July 2016. We compared Wip1-knockout (Wip1-KO) mice and wild-type (WT) mice to determine changes in cardiac function and survival in response to MI...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28440479/wip1-regulates-skov3-cell-apoptosis-through-the-p38-mapk-signaling-pathway
#15
Yanping Feng, Fang Liu, Zhixiang Du, Dongjie Zhao, Jianxin Cheng, Wei Guo
The aim of the present study was to explore the effect of silencing wild‑type p53‑induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase‑3, caspase‑3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl‑2), p38 mitogen‑activated protein kinase (p38 MAPK) and phosphorylated (p)‑p38 MAPK...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439615/wip1-phosphatase-as-pharmacological-target-in-cancer-therapy
#16
REVIEW
Soňa Pecháčková, Kamila Burdová, Libor Macurek
DNA damage response (DDR) pathway protects cells from genome instability and prevents cancer development. Tumor suppressor p53 is a key molecule that interconnects DDR, cell cycle checkpoints, and cell fate decisions in the presence of genotoxic stress. Inactivating mutations in TP53 and other genes implicated in DDR potentiate cancer development and also influence the sensitivity of cancer cells to treatment. Protein phosphatase 2C delta (referred to as WIP1) is a negative regulator of DDR and has been proposed as potential pharmaceutical target...
June 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28417973/excitability-in-the-p53-network-mediates-robust-signaling-with-tunable-activation-thresholds-in-single-cells
#17
Gregor Mönke, Elena Cristiano, Ana Finzel, Dhana Friedrich, Hanspeter Herzel, Martin Falcke, Alexander Loewer
Cellular signaling systems precisely transmit information in the presence of molecular noise while retaining flexibility to accommodate the needs of individual cells. To understand design principles underlying such versatile signaling, we analyzed the response of the tumor suppressor p53 to varying levels of DNA damage in hundreds of individual cells and observed a switch between distinct signaling modes characterized by isolated pulses and sustained oscillations of p53 accumulation. Guided by dynamic systems theory we show that this requires an excitable network structure comprising positive feedback and provide experimental evidence for its molecular identity...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28417018/dna-damage-induced-phosphatase-wip1-in-regulation-of-hematopoiesis-immune-system-and-inflammation
#18
REVIEW
B Uyanik, B B Grigorash, A R Goloudina, O N Demidov
PP2C serine-threonine phosphatase, Wip1, is an important regulator of stress response. Wip1 controls a number of critical cellular functions: proliferation, cell cycle arrest, senescence and programmed cell death, apoptosis or autophagy. Ppm1d, the gene encoding Wip1 phosphatase, is expressed in hematopoietic progenitors, stem cells, neutrophils, macrophages B and T lymphocytes in bone marrow and peripheral blood. The Wip1-/- mice display immunodeficiency, abnormal lymphoid histopathology in thymus and spleen, defects in B- and T-cell differentiation, as well as susceptibility to viral infection...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28402943/expression-of-wild-type-p53-induced-phosphatase-1-in-diabetic-epiretinal-membranes
#19
Jiping Xu, Haibin Zhong, Ling Cui, Qianqian Lan, Lifei Chen, Wenjing He, Yu Wu, Li Jiang, Hui Huang, Xin Zhao, Li Li, Siming Zeng, Min Li, Fan Xu
OBJECTIVE: The aims of the present study were to investigate the expression and distribution of Wild-type p53-induced phosphatase 1 (Wip1) in diabetic patients with proliferative diabetic retinopathy (PDR) with epiretinal membranes (ERMs) meanwhile analyze the colocalization of Wip1 and nuclear factor kappa-B (NF-κB) p65 in ERMs. METHODS: ERMs samples were collected from patients with PDR (PDR group) or non-diabetic patients with idiopathic epiretinal membranes (iERMs) (control group) during pars plana vitrectomy...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28385459/wip1-a-candidate-phosphatase-for-cancer-diagnosis-and-treatment
#20
REVIEW
Tayebeh Oghabi Bakhshaiesh, Keivan Majidzadeh-A, Rezvan Esmaeili
The critical regulatory mechanisms in numerous cellular pathways including cell survival and DNA damage response mostly depend on phosphorylation and dephosphorylation of proteins. The serine/threonine phosphatase wild-type p53-induced phosphatase 1 (Wip1) is a growth-promoting phosphatase and its numerous downstream targets are important tumor suppressors. Here, we review the Wip1 activity and its relevance to cancer as an oncoprotein. Consecutive investigations about Wip1 and its relation to cancer is critical, as these studies ultimately contribute to the etiology of cancer...
June 2017: DNA Repair
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