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https://www.readbyqxmd.com/read/29147820/cue-signal-response-analysis-in-3d-chondrocyte-scaffolds-with-anabolic-stimuli
#1
Michael Neidlin, Antonion Korcari, Giorgos Macheras, Leonidas G Alexopoulos
Articular cartilage is an avascular connective tissue responsible for bearing loads. Cell signaling plays a central role in cartilage homeostasis and tissue engineering by directing chondrocytes to synthesize/degrade the extracellular matrix or promote inflammatory responses. The aim of this paper was to investigate anabolic, catabolic and inflammatory pathways of well-known and underreported anabolic stimuli in 3D chondrocyte cultures and connect them to diverse cartilage responses including matrix regeneration and cell communication...
November 16, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29134279/dietary-k-and-cl-independently-regulate-basolateral-conductance-in-principal-and-intercalated-cells-of-the-collecting-duct
#2
Viktor N Tomilin, Oleg Zaika, Arohan R Subramanya, Oleh Pochynyuk
The renal collecting duct contains two distinct cell types, principal and intercalated cells, expressing potassium Kir4.1/5.1 (KCNJ10/16) and chloride ClC-K2 (ClC-Kb in humans) channels on their basolateral membrane, respectively. Both channels are thought to play important roles in controlling systemic water-electrolyte balance and blood pressure. However, little is known about mechanisms regulating activity of Kir4.1/5.1 and ClC-K2/b. Here, we employed patch clamp analysis at the single channel and whole cell levels in freshly isolated mouse collecting ducts to investigate regulation of Kir4...
November 13, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29049855/intra-arterial-transplantation-of-human-bone-marrow-mesenchymal-stem-cells-hbmmscs-improves-behavioral-deficits-and-alters-gene-expression-in-rodent-stroke-model
#3
Vibhuti, Rehan Khan, Alpana Sharma, Suman Jain, Sujata Mohanty, Kameshwar Prasad
Stroke is a multi-factorial polygenic disease and is a major cause of death and adult disability. Administration of bone marrow stem cells protects ischemic rat brain by facilitating recovery of neurological functions. But the molecular mechanism of stem cells action and their effect on gene expression is not well explored. In this study, we have transplanted 1× 10(6) human bone marrow mesenchymal stem cells (hBMMSCs) in middle cerebral artery occluded (MCAo) adult male Wistar rats through intracarotid artery route at 24 hours after surgery...
October 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29029515/discovery-of-nkcc1-as-a-potential-therapeutic-target-to-inhibit-hepatocellular-carcinoma-cell-growth-and-metastasis
#4
Yaya Zhou, Wei Sun, Ning Chen, Chen Xu, Xinxin Wang, Kun Dong, Binxue Zhang, Jian Zhang, Ning Hao, Aihua Sun, Handong Wei, Fuchu He, Ying Jiang
Metastasis is the essential cause for the high mortality of hepatocellular carcinoma (HCC). In order to investigate the mechanism of metastasis, and to discover therapeutic targets for HCC, the quantitative proteomic technique was applied to characterize the plasma membrane proteins of two HCC cell lines with low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1 expression was associated with poor differentiation and microvascular invasion...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29025069/wnk-lysine-deficient-protein-kinase-1-regulates-human-endometrial-stromal-cell-decidualization-proliferation-and-migration-in-part-through-mitogen-activated-protein-kinase-7
#5
Nyssa R Adams, Yasmin M Vasquez, Qianxing Mo, William Gibbons, Ertug Kovanci, Francesco J DeMayo
The differentiation of endometrial stromal cells into decidual cells, termed decidualization, is an integral step in the establishment of pregnancy. The mitogen-activated protein kinase homolog, WNK lysine deficient protein kinase 1 (WNK1), is activated downstream of epidermal growth factor receptor during decidualization. Primary human endometrial stromal cells (HESCs) were subjected to small interfering RNA knockdown of WNK1 followed by in vitro decidualization. This abrogated expression of the decidual marker genes, insulin like growth factor binding protein 1 (IGFBP1) and prolactin (PRL), and prevented adoption of decidual cell morphology...
September 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28969913/genetic-predisposition-to-bevacizumab-induced-hypertension
#6
Melissa K Frey, Fanny Dao, Narciso Olvera, Jason A Konner, Maura N Dickler, Douglas A Levine
OBJECTIVE: Bevacizumab, a monoclonal antibody to VEGF, has shown efficacy in ovarian, cervical and endometrial cancer in addition to several other solid tumors. Serious side effects include hypertension, proteinuria, bowel perforation, and thrombosis. We tested the hypothesis that genetic variation in hypertension-associated genes is associated with bevacizumab-induced hypertension (BIH). METHODS: Patients with solid tumors treated with bevacizumab in combination with other therapy were identified from six clinical trials...
September 29, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28969021/secreted-protein-acidic-and-rich-in-cysteine-sparc-induces-cell-migration-and-epithelial-mesenchymal-transition-through-wnk1-snail-in-non-small-cell-lung-cancer
#7
Jen-Yu Hung, Meng-Chi Yen, Shu-Fang Jian, Cheng-Ying Wu, Wei-An Chang, Kuan-Ting Liu, Ya-Ling Hsu, Inn-Wen Chong, Po-Lin Kuo
The extracellular matrix is a component of physiological microenvironment and a regulator of cellular processes such as migration and proliferation. Secreted Protein Acidic and Rich in Cysteine (SPARC/osteonectin) is an extracellular matrix-associated glycoprotein involved in the regulation of cell proliferation and cell migration in several types of cancers. However, the role of SPARC in lung cancer is paradoxical and details of the regulatory mechanism are not well-known. In this study, we investigated novel SPARC-mediated signaling pathways...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28945285/association-of-with-no-lysine-kinase-1-and-serine-threonine-kinase-39-gene-polymorphisms-and-haplotypes-with-essential-hypertension-in-tibetans
#8
Rufeng Shi, Jiangbo Li, Jiyun He, Qingtao Meng, Zhiping Qian, Di Shi, Qi Liu, Yali Cai, Xinran Li, Xiaoping Chen
Tibetans have a higher essential hypertension prevalence compared with other ethnics in China. The reason might be due to their unique environmental influence, as well as genetic factor. However, limited studies focus on Tibetan genetics and its association with hypertension. The aim of this study was to investigate the association between With-No-Lysine (K) Kinase 1 (WNK1), Serine/Threonine kinase 39(STK39) genes variants and hypertension in the Tibetan population. 204 Tibetan hypertensive patients and 305 normotensive controls were recruited in an epidemiological survey conducted at 2 sites in the Ganzi Tibetan autonomous region...
September 25, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28915228/analysis-of-the-genes-involved-in-mendelian-forms-of-low-renin-hypertension-in-chinese-early-onset-hypertensive-patients
#9
Kai Liu, Fang Qin, Xiaolu Sun, Yang Zhang, Jizheng Wang, Yajie Wu, Wenjun Ma, Wei Wang, Xueyi Wu, Ying Qin, Huimin Zhang, Xianliang Zhou, Haiying Wu, Rutai Hui, Yubao Zou, Xiongjing Jiang, Lei Song
BACKGROUND: The study aimed to analyze genes involved in Mendelian forms of low-renin hypertension in Chinese early-onset hypertensive patients. METHODS: A panel of nine genes, namely SCNN1B, SCNN1G, WNK1, WNK4, KLHL3, CUL3, nuclear receptor subfamily 3, group C (NR3C)1, NR3C2, and HSD11B2 were screened by targeted resequencing in 260 Chinese early-onset hypertensive patients. Additionally, exon 13 of both SCNN1B and SCNN1G was sequenced in an independent cohort of 506 Chinese early-onset hypertensive patients...
September 14, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28819369/in-vitro-cytotoxic-activities-of-the-oral-platinum-iv-prodrug-oxoplatin-and-hsp90-inhibitor-ganetespib-against-a-panel-of-gastric-cancer-cell-lines
#10
Lukas Klameth, Barbara Rath, Gerhard Hamilton
Gastric cancer exhibits a poor prognosis and is the third most common cause of cancer death worldwide. Chemotherapy of metastatic gastric cancer is based on combinations of platinum drugs and fluoropyrimidines, with added agents. Oxoplatin is a stable oral platinum(IV) prodrug which is converted to a highly active tetrachlorido(IV) complex under acidic conditions. In the present work, we studied the cytotoxic effects of oxoplatin against a panel of four gastric cancer cell lines in vitro. Furthermore, the role of HSP90 in chemoresistance of these lines was investigated using the specific inhibitor ganetespib...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28771350/optimization-of-allosteric-with-no-lysine-wnk-kinase-inhibitors-and-efficacy-in-rodent-hypertension-models
#11
Ken Yamada, Julian Levell, Taeyong Yoon, Darcy Kohls, David Yowe, Dean F Rigel, Hidetomo Imase, Jun Yuan, Kayo Yasoshima, Keith DiPetrillo, Lauren Monovich, Lingfei Xu, Meicheng Zhu, Mitsunori Kato, Monish Jain, Neeraja Idamakanti, Paul Taslimi, Toshio Kawanami, Upendra A Argikar, Vidya Kunjathoor, Xiaoling Xie, Yukiko I Yagi, Yuki Iwaki, Zachary Robinson, Hyi-Man Park
The observed structure-activity relationship of three distinct ATP noncompetitive With-No-Lysine (WNK) kinase inhibitor series, together with a crystal structure of a previously disclosed allosteric inhibitor bound to WNK1, led to an overlay hypothesis defining core and side-chain relationships across the different series. This in turn enabled an efficient optimization through scaffold morphing, resulting in compounds with a good balance of selectivity, cellular potency, and pharmacokinetic profile, which were suitable for in vivo proof-of-concept studies...
August 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28770829/wnk1-is-required-for-proliferation-induced-by-hypotonic-challenge-in-rat-vascular-smooth-muscle-cells
#12
Ya-Juan Zhang, Hua-Qing Zheng, Bao-Yi Chen, Lu Sun, Ming-Ming Ma, Guan-Lei Wang, Yong-Yuan Guan
Hypotonic challenge evoked vascular cell proliferation through activation of volume-regulated Cl(-) channel (VRCC), leading to a decrease in the intracellular Cl(-) concentration ([Cl(-)]i). We hypothesize that the decrease in [Cl(-)]i may activate one or several Cl(-)-sensitive kinases, resulting in a subsequent signaling cascade. In this study we demonstrated that WNK1, a Cl(-)-sensitive kinase, was involved in VRCC-induced proliferative signaling pathway in A10 vascular smooth muscle cells in vitro. A10 cells were exposed to a hypotonic challenge (225 mosmol·kg(-1)·H20), which caused significantly increase in WNK1 phosphorylation without altering WNK1 protein expression...
August 3, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28743496/wnk4-is-indispensable-for-the-pathogenesis-of-pseudohypoaldosteronism-type-ii-caused-by-mutant-klhl3
#13
Koichiro Susa, Eisei Sohara, Daiei Takahashi, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida
WNK-OSR1/SPAK-NCC signaling cascade is important for regulating salt balance and blood pressure. Activation of WNK-OSR1/SPAK-NaCl cotransporter (NCC) cascade increases sodium reabsorption in the kidney, leading to pseudohypoaldosteronism type II (PHA II) characterized by salt-sensitive hypertension and hyperkalemia. It has been previously demonstrated that the amount of phosphorylated and total NCC markedly decreased in WNK4(-/-) mice, indicating that WNK4 plays a major role for activation of OSR1/SPAK-NCC signaling...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28679620/integrated-single-cell-genetic-and-transcriptional-analysis-suggests-novel-drivers-of-chronic-lymphocytic-leukemia
#14
Lili Wang, Jean Fan, Joshua M Francis, George Georghiou, Sarah Hergert, Shuqiang Li, Rutendo Gambe, Chensheng W Zhou, Chunxiao Yang, Sheng Xiao, Paola Dal Cin, Michaela Bowden, Dylan Kotliar, Sachet A Shukla, Jennifer R Brown, Donna Neuberg, Dario R Alessi, Cheng-Zhong Zhang, Peter V Kharchenko, Kenneth J Livak, Catherine J Wu
Intra-tumoral genetic heterogeneity has been characterized across cancers by genome sequencing of bulk tumors, including chronic lymphocytic leukemia (CLL). In order to more accurately identify subclones, define phylogenetic relationships, and probe genotype-phenotype relationships, we developed methods for targeted mutation detection in DNA and RNA isolated from thousands of single cells from five CLL samples. By clearly resolving phylogenic relationships, we uncovered mutated LCP1 and WNK1 as novel CLL drivers, supported by functional evidence demonstrating their impact on CLL pathways...
August 2017: Genome Research
https://www.readbyqxmd.com/read/28672809/montelukast-induces-apoptosis-inducing-factor-mediated-cell-death-of-lung-cancer-cells
#15
Ming-Ju Tsai, Wei-An Chang, Pei-Hsun Tsai, Cheng-Ying Wu, Ya-Wen Ho, Meng-Chi Yen, Yi-Shiuan Lin, Po-Lin Kuo, Ya-Ling Hsu
Developing novel chemo-prevention techniques and advancing treatment are key elements to beating lung cancer, the most common cause of cancer mortality worldwide. Our previous cohort study showed that cysteinyl leukotriene receptor antagonists, mainly montelukast, decreased the lung cancer risk in asthma patients. In the current study, we conducted in vivo and in vitro experiments to demonstrate the inhibiting effect of montelukast on lung cancer and to investigate the underlying mechanisms. Using Lewis lung carcinoma-bearing mice, we showed that feeding montelukast significantly delayed the tumor growth in mice (p < 0...
June 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28596815/next-generation-sequencing-traces-human-induced-pluripotent-stem-cell-lines-clonally-generated-from-heterogeneous-cancer-tissue
#16
Tetsuya Ishikawa
AIM: To investigate genotype variation among induced pluripotent stem cell (iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. METHODS: Human iPSC lines were clonally established by selecting independent single colonies expanded from heterogeneous primary cells of S-shaped colon cancer tissues by retroviral gene transfer (OCT3/4, SOX2, and KLF4). The ten iPSC lines, their starting cancer tissues, and the matched adjacent non-cancerous tissues were analyzed using next-generation sequencing and bioinformatics analysis using the human reference genome hg19...
May 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28522431/wnk1-and-p38-mapk-distribution-in-ionocytes-and-accessory-cells-of-euryhaline-teleost-fish-implies-ionoregulatory-function
#17
W S Marshall, R R F Cozzi, M Spieker
Ionocytes of euryhaline teleost fish secrete NaCl, under regulation by serine and threonine kinases, including with-no-lysine kinase (WNK1) and p38 mitogen-activated protein kinase (MAPK). Mummichogs (Fundulus heteroclitus L.) were acclimated to freshwater (FW), full strength seawater (SW) and hypersaline conditions (2SW). Immunocytochemistry of ionocytes in opercular epithelia of fish acclimated to SW and 2SW revealed that WNK1-anti-pT58 phosphoantibody localized strongly to accessory cells and was present in the cytosol of ionocytes, close to cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane and the sodium potassium 2 chloride cotransporter (NKCC) in the basolateral membrane...
July 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28511177/familial-hyperkalemia-and-hypertension-fhht-and-klhl3-description-of-a-family-with-a-new-recessive-mutation-s553l-compared-to-a-family-with-a-dominant-mutation-q309r-with-analysis-of-urinary-sodium-chloride-cotransporter
#18
Orit Kliuk-Ben Bassat, Vered Carmon, Aaron Hanukoglu, Liat Ganon, Eias Massalha, Eliezer J Holtzman, Zvi Farfel, Haim Mayan
BACKGROUND: Familial hyperkalemia and hypertension (FHHt) is an inherited disorder manifested by hyperkalemia and hypertension. The following four causative genes were identified: WNK1, WNK4, CUL3, and KLHL3. For the first 3 genes, inheritance is autosomal dominant. For KLHL3, inheritance is mostly dominant. A few cases with autosomal recessive disease were described. The mechanism of these 2 modes of inheritance is not clear. In the recessive form, the phenotype of heterozygotes is not well described...
2017: Nephron
https://www.readbyqxmd.com/read/28489665/the-nogo-receptor-inhibits-proliferation-migration-and-axonal-extension-by-transcriptionally-regulating-wnk1-in-pc12-cells
#19
Tao Yang, Kai Zhao, Haifeng Shu, Xin Chen, Jingmin Cheng, Song Li, Ziyi Zhao, Yongqin Kuang, Sixun Yu
Neuronal regeneration and axonal regrowth mechanisms in the injured mammalian central nervous system are largely unknown. As part of a major pathway for inhibiting axonal regeneration, activated neuronal glycosylphosphatidylinositol-anchored Nogo receptor (NgR) interacts with LINGO-1 and p75NTR to form a complex at the cell surface. However, it was found in our previous report that upregulation of NgR stimulated by injury plays a key role in neuronal regeneration in the neonatal cortex freeze-lesion model, but its downstream signalling remains elusive...
June 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28422281/wnk1-hsn2-founder-mutation-in-patients-with-hereditary-sensory-and-autonomic-neuropathy-a-japanese-cohort-study
#20
J-H Yuan, A Hashiguchi, A Yoshimura, N Sakai, M P Takahashi, T Ueda, A Taniguchi, S Okamoto, N Kanazawa, Y Yamamoto, K Saigoh, S Kusunoki, M Ando, Y Hiramatsu, Y Okamoto, H Takashima
The clinical and genetic spectrum of hereditary sensory and autonomic neuropathy (HSAN) is still unknown in Japan. We collected a broad cohort of 33 unrelated patients with predominant sensory and/or autonomic dysfunctions, who were referred to our genetic laboratory. A gene panel sequencing targeting 18 HSAN-related genes was performed using a next-generation sequencing system. A recurrent frame shift mutation in the WNK1/HSN2 gene, c.3237_3238insT (p.Asp1080*), was detected in 5 patients. This mutation was homozygous in 4 cases and of a compound heterozygous genotype in 1 case...
April 19, 2017: Clinical Genetics
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