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Integrin linked kinase

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https://www.readbyqxmd.com/read/28630423/thymosin-beta-4-regulates-activation-of-hepatic-stellate-cells-via-hedgehog-signaling
#1
Jieun Kim, Jeongeun Hyun, Sihyung Wang, Chanbin Lee, Jae-Wook Lee, Eun-Yi Moon, Heejae Cha, Anna Mae Diehl, Youngmi Jung
The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA-treated LX-2. TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615322/in-vivo-manipulation-of-the-extracellular-matrix-induces-vascular-regression-in-a-basal-chordate
#2
Delany Rodriguez, Brian P Braden, Scott W Boyer, Daryl A Taketa, Leah Setar, Chris Calhoun, Alessandro Di Maio, Adam Langenbacher, Megan T Valentine, Anthony W De Tomaso
We investigated the physical role of the extracellular matrix in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent extracorporeal vascular network encompassing areas >100 cm(2) We found that the collagen crosslinking enzyme lysyl oxidase is expressed in all vascular cells, and that in vivo inhibition using ß-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 hours. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose-dependent...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28578803/head-and-neck-cancer-cell-radiosensitization-upon-dual-targeting-of-c-abl-and-beta1-integrin
#3
Philipp Koppenhagen, Ellen Dickreuter, Nils Cordes
Integrin-mediated cell adhesion to extracellular matrix (ECM) critically contributes to cancer cell therapy resistance and DNA double strand break (DSB) repair. c-Abl tyrosine kinase has been linked to both of these processes. Based on our previous findings indicating c-Abl hyperphosphorylation on tyrosine (Y) 412 and threonine (T) 735 upon beta1-integrin inhibition, we hypothesized c-Abl tyrosine kinase as an important mediator of beta1-integrin signaling for radioresistance. In a panel of 8 cell lines from different solid cancer types grown in 3D laminin-rich ECM cultures, we targeted beta1 integrin with AIIB2 (mAb) and c-Abl with Imatinib with and without X-ray irradiation and subsequently examined clonogenic survival, residual DSBs, protein expression and phosphorylation...
May 31, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28577299/upa-upar-system-activation-drives-a-glycolytic-phenotype-in-melanoma-cells
#4
Anna Laurenzana, Anastasia Chillà, Cristina Luciani, Silvia Peppicelli, Alessio Biagioni, Francesca Bianchini, Elena Tenedini, Eugenio Torre, Alessandra Mocali, Lido Calorini, Francesca Margheri, Gabriella Fibbi, Mario Del Rosso
In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells...
June 2, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28576970/low-intensity-pulsed-ultrasound-lipus-promotes-cell-motility-through-vinculin-controlled-rac1-gtpase-activity
#5
Paul Atherton, Franziska Lausecker, Andrew Harrison, Christoph Ballestrem
Low Intensity Pulsed Ultrasound (LIPUS) is a therapy used clinically to promote healing. Using live cell imaging we show that LIPUS stimulation, acting through integrin-mediated cell-matrix adhesions, rapidly induces Rac activation associated with dramatic actin cytoskeleton rearrangements. Our study demonstrates that the mechanosensitive focal adhesion (FA) protein vinculin and both Focal Adhesion Kinase (FAK) and Rab5 have key roles in regulating these effects. Inhibiting the link of vinculin to the actin-cytoskeleton abolished LIPUS sensing...
June 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28574598/integrin-linked-kinase-regulates-bone-formation-by-controlling-cytoskeletal-organization-and-modulating-bmp-and-wnt-signaling-in-osteoprogenitors
#6
Marian Dejaeger, Anna-Marei Böhm, Naomi Dirckx, Joke Devriese, Elena Nefyodova, Ruben Cardoen, René St-Arnaud, Jos Tournoy, Frank P Luyten, Christa Maes
Cell-matrix interactions constitute a fundamental aspect of skeletal cell biology and play essential roles in bone homeostasis. These interactions are primarily mediated by transmembrane integrin receptors, which mediate cell adhesion and transduce signals from the extracellular matrix to intracellular responses via various downstream effectors, including integrin-linked kinase (ILK). ILK functions as adaptor protein at focal adhesion sites, linking integrins to the actin cytoskeleton, and has been reported to act as a kinase phosphorylating signaling molecules such as GSK-3β and Akt...
June 2, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28565830/correlation-between-pkb-akt-gsk-3%C3%AE-expression-and-tubular-epithelial-mesenchymal-transition-in-renal-allografts-with-chronic-active-antibody-mediated-rejection
#7
Qiang Yan, Hao Luo, Baoyao Wang, Weiguo Sui, Guimian Zou, Huaizhou Chen, Hequn Zou
Chronic antibody-mediated rejection (ABMR) is a major cause of the transplant renal interstitial fibrosis and transplanted kidney epithelial cell transdifferentiation is one of the main mechanisms. The transforming growth factor (TGF)-β1/integrin-linked kinase (ILK) signaling pathway has a significant role in the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells; however, the molecular mechanisms of this process have remained elusive. The present study confirmed that Akt and glycogen synthase kinase (GSK)-3β, as TGF-β1 downstream signaling factors, are involved in fibrotic processes caused by kidney disease, which, however, has been rarely reported in the kidney transplant field...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28565779/expression-of-integrin-linked-kinase-improves-cardiac-function-in-a-swine-model-of-myocardial-infarction
#8
Wen Lu, Jun Xie, Rong Gu, Biao Xu
Previous studies have described the beneficial effects of overexpressing integrin-linked kinase (ILK) after myocardial infarction (MI) in small animal models. However, the effects of ILK in pre-clinical large animals are not known. To move closer to clinical translation, we examined the effects of ILK gene transfer in a swine model of ischemic heart disease. Swine received percutaneous intracoronary injections of adenoviral vector expressing ILK (n=10) or empty ad-null (n=10) in the left anterior descending coronary artery (LAD) following LAD occlusion...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28546219/inos-derived-nitric-oxide-induces-integrin-linked-kinase-endocytic-lysosome-mediated-degradation-in-the-vascular-endothelium
#9
Paula Reventun, Matilde Alique, Irene Cuadrado, Susana Marquez, Rocio Toro, Carlos Zaragoza, Marta Saura
OBJECTIVE: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. APPROACH AND RESULTS: We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with inducible NO synthase knockout mice...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28522687/integrin-linked-kinase-signaling-promotes-cyst-growth-and-fibrosis-in-polycystic-kidney-disease
#10
Archana Raman, Gail A Reif, Yuqiao Dai, Aditi Khanna, Xiaogang Li, Lindsay Astleford, Stephen C Parnell, James P Calvet, Darren P Wallace
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin...
May 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28490443/peripheral-insulin-resistance-in-ilk-depleted-mice-by-reduction-of-glut4-expression
#11
Marco Hatem-Vaquero, Mercedes Griera, Andrea Garcia-Jerez, Alicia Luengo, Julia Alvarez-Hernandez, Jose Antonio Rubio-Garcia, Laura Calleros, Diego Rodriguez-Puyol, Manuel Rodriguez-Puyol, Sergio de Frutos
The development of insulin resistance is characterized by the impairment of glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix changes are induced when the metabolic dysregulation is sustained. The present work was devoted to analyze the possible link between the extracellular-to-intracellular mediator integrin linked kinase (ILK) and the peripheral tissue modification that leads to glucose homeostasis impairment. Mice with general depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited increased glycaemia and insulinemia concurrently with a reduction of the expression and membranes presence of GLUT4 in the insulin-sensitive peripheral tissues compared with their wildtype littermates (WT)...
May 10, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28476896/altered-cargo-proteins-of-human-plasma-endothelial-cell-derived-exosomes-in-atherosclerotic-cerebrovascular-disease
#12
Edward J Goetzl, Janice B Schwartz, Maja Mustapic, Iryna V Lobach, Richard Daneman, Erin L Abner, Gregory A Jicha
Plasma endothelial cell-derived exosomes (EDEs) and platelet-derived exosomes (PDEs) were precipitated and enriched separately by immunospecific absorption procedures for analyses of cargo proteins relevant to atherosclerosis. EDEs had usual exosome size and marker protein content, and significantly higher levels than PDEs of the endothelial proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase, whereas PDEs had significantly higher levels of platelet glycoprotein VI. EDE levels of VCAM-1, von Willebrand factor, platelet-derived growth factor (PDGF)-BB, angiopoietin-1, and lysyl oxidase-2 and the cerebrovascular-selective proteins glucose transporter 1, permeability-glycoprotein, and large neutral amino acid transporter 1 were significantly higher for 18 patients with cerebrovascular disease (CeVD) than for 18 age- and gender-matched control subjects...
May 5, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28464379/activation-of-transforming-growth-factor-%C3%AE-1-by-thrombin-via-integrins-%C3%AE-v%C3%AE-1-%C3%AE-v%C3%AE-3-and-%C3%AE-v%C3%AE-5-in-buccal-fibroblasts-suppression-by-epigallocatechin-3-gallate
#13
Jenny Zwei-Chieng Chang, Yu-Ping Hsieh, Wen-Hsin Lin, Hsin-Ming Chen, Mark Yen-Ping Kuo
BACKGROUND: Transforming growth factor-beta (TGF-β) plays a central role in the pathogenesis of oral submucous fibrosis (OSF). Thrombin is a key player in tissue repair, inflammation, and fibrosis after injury. METHODS: Effects of thrombin on activated-TGF-β1 levels, Smad3 phosphorylation, and connective tissue growth factor (CTGF/CCN2) synthesis in primary human buccal mucosal fibroblasts (BMFs) were assessed by enzyme-linked immunosorbent assay or Western blot analysis...
May 2, 2017: Head & Neck
https://www.readbyqxmd.com/read/28459432/metformin-inhibits-suv39h1-mediated-migration-of-prostate-cancer-cells
#14
T Yu, C Wang, J Yang, Y Guo, Y Wu, X Li
Prostate cancer (PCa) is a leading cause of cancer-related death among men, largely due to incurable distant metastases. Metformin, the most common used anti-type-2 diabetes medicine, has been linked to reduced cancer risk and better diagnosis. We found that metformin was able to inhibit PCa cell migration, which correlates with tumor metastatic capability. The pathogenesis and progression of tumors are closely related to dysregulated gene expression in tumor cells through epigenetic alterations such as DNA methylation and histone modifications...
May 1, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28421082/insights-into-the-structure-function-and-ion-mediated-signaling-pathways-transduced-by-plant-integrin-linked-kinases
#15
Sorina C Popescu, Elizabeth K Brauer, Gizem Dimlioglu, George V Popescu
Kinases facilitate detection of extracellular signals and set in motion cellular responses for plant adaptation and survival. Some of the energy utilized for kinase signal processing is produced through the activity of ion transporters. Additionally, the synergy between cellular ions and signal transduction influences plant response to pathogens, and their growth and development. In plants, the signaling elements that connect cell wall and membrane sensors with ion homeostasis and transport-mediated processes are largely unknown...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28413908/molecular-mechanisms-involved-in-podocyte-emt-and-concomitant-diabetic-kidney-diseases-an-update
#16
Qidi Ying, Guanzhong Wu
Epithelial-mesenchymal transition (EMT) is a tightly regulated process by which epithelial cells lose their hallmark epithelial characteristics and gain the features of mesenchymal cells. For podocytes, expression of nephrin, podocin, P-cadherin, and ZO-1 is downregulated, the slit diaphragm (SD) will be altered, and the actin cytoskeleton will be rearranged. Diabetes, especially hyperglycemia, has been demonstrated to incite podocyte EMT through several molecular mechanisms such as TGF-β/Smad classic pathway, Wnt/β-catenin signaling pathway, Integrins/integrin-linked kinase (ILK) signaling pathway, MAPKs signaling pathway, Jagged/Notch signaling pathway, and NF-κB signaling pathway...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28404615/myeloperoxidase-mediates-postischemic-arrhythmogenic-ventricular-remodeling
#17
Martin Mollenhauer, Kai Friedrichs, Max Lange, Jan Gesenberg, Lisa Remane, Christina Kerkenpaß, Jenny Krause, Johanna Schneider, Thorben Ravekes, Martina Maass, Marcel Halbach, Gabriel Peinkofer, Tomo Saric, Dennis Mehrkens, Matti Adam, Florian G Deuschl, Denise Lau, Birgit Geertz, Kashish Manchanda, Thomas Eschenhagen, Lukas Kubala, Tanja K Rudolph, Yuping Wu, W H Wilson Tang, Stanley L Hazen, Stephan Baldus, Anna Klinke, Volker Rudolph
RATIONALE: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. OBJECTIVE: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. METHODS AND RESULTS: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection...
June 23, 2017: Circulation Research
https://www.readbyqxmd.com/read/28391962/su9516-increases-%C3%AE-7%C3%AE-1-integrin-and-ameliorates-disease-progression-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy
#18
Apurva Sarathy, Ryan D Wuebbles, Tatiana M Fontelonga, Ashley R Tarchione, Lesley A Mathews Griner, Dante J Heredia, Andreia M Nunes, Suzann Duan, Paul D Brewer, Tyler Van Ry, Grant W Hennig, Thomas W Gould, Andrés E Dulcey, Amy Wang, Xin Xu, Catherine Z Chen, Xin Hu, Wei Zheng, Noel Southall, Marc Ferrer, Juan Marugan, Dean J Burkin
Duchenne muscular dystrophy (DMD) is a fatal muscle disease caused by mutations in the dystrophin gene, resulting in a complete loss of the dystrophin protein. Dystrophin is a critical component of the dystrophin glycoprotein complex (DGC), which links laminin in the extracellular matrix to the actin cytoskeleton within myofibers and provides resistance to shear stresses during muscle activity. Loss of dystrophin in DMD patients results in a fragile sarcolemma prone to contraction-induced muscle damage. The α7β1 integrin is a laminin receptor protein complex in skeletal and cardiac muscle and a major modifier of disease progression in DMD...
June 7, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28339614/integrin-linked-kinase-regulates-syncytialization-of-bewo-trophoblast-cells%C3%A2
#19
Trina M Butler, Justin A Pater, Daniel J MacPhee
During placental development, mononuclear villous cytotrophoblast cells differentiate and fuse with the overlying syncytiotrophoblast. This process requires the dissolution of E-cadherin (CDH1)-containing adherens junctions in cytotrophoblast. Integrin linked kinase (ILK) can downregulate CDH1 through poly (ADP-ribose) polymerase 1 (PARP1) and Snail-1 (SNAI1) during epithelial-mesenchymal transition. ILK is known to be expressed in cytotrophoblast; thus, the role of a potential ILK-PARP1-SNAI1 pathway in aiding trophoblast syncytialization via the downregulation of CDH1 was examined...
March 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28325807/tensin-links-energy-metabolism-to-extracellular-matrix-assembly
#20
Emmanuel Dornier, Jim C Norman
The regulation of integrin function is key to fundamental cellular processes, including cell migration and extracellular matrix (ECM) assembly. In this issue, Georgiadou et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201609066) report that the metabolic sensor adenosine monophosphate-activated protein kinase influences tensin production to regulate α5β1-integrin and fibrillar adhesion assembly and thus reveal an important connection between energy metabolism and ECM assembly.
April 3, 2017: Journal of Cell Biology
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