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Integrin linked kinase

Lishan Jia, Xiaozhong Li, Yueqin Gu, Weifeng Cui
BACKGROUND: Despite a previous study showing that PINCH-1 exerts an important role in regulating TGF-β1-mediated mesenchymal transition through its interaction with integrin-linked kinase, relatively little is known about the role of PINCH in the obstructive nephropathy. METHODS: To construct a rat model of renal interstitial fibrosis and obstructive nephropathy, unilateral ureteral obstruction (UUO) was used. Hematoxylin and eosin and Masson staining were used in histologic examinations...
October 22, 2016: American Journal of Nephrology
Yuhang Zhou, Shaji Abraham, Stephanie Renna, Leonard C Edelstein, Carol A Dangelmaier, Alexander Y Tsygankov, Satya P Kunapuli, Paul F Bray, Steven E McKenzie
OBJECTIVE: The objective of this study is to investigate the role of T-cell ubiquitin ligand-2 (TULA-2) in the platelet Fc receptor for IgG IIA (FcγRIIA) pathway and in the pathogenesis of heparin-induced thrombocytopenia (HIT). APPROACH AND RESULTS: HIT is a life-threatening thrombotic disease in which IgG antibodies against the heparin-platelet factor 4 complex activate platelets via FcγRIIA. We reported previously differential expression of TULA-2 in human population was linked to FcγRIIA responsiveness...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Fahmy A Mamuya, Jose Luis Cano-Peñalver, Wei U Li, Diego Rodriguez-Puyol, Manuel Rodríguez-Puyol, Dennis Brown, Sergio de Frutos, Hua Jenny Lu
Within the past decade tremendous efforts have been made to understand the mechanism behind aquaporin-2 (AQP2) water channel trafficking and recycling, in order to open a path towards effective diabetes insipidus therapeutics. A recent study has shown that Integrin-Linked Kinase (ILK) conditional-knockdown mice developed polyuria along with decreased expression of AQP2. To understand whether ILK also regulates AQP2 trafficking in kidney tubular cells, we performed in vitro analysis using LLCPK1 cells stably expressing rat AQP2 (LLC-AQP2 cells)...
October 19, 2016: American Journal of Physiology. Renal Physiology
Yi Li, Xiaoli Shi, Lei Tian, Hongyu Sun, Yujing Wu, Xia Li, Jianjun Li, Yujie Wei, Xinxiao Han, Jiao Zhang, Xiaowei Jia, Rui Bai, Limin Jing, Peng Ding, Huiliang Liu, Dong Han
A schematic for the mechanism of accelerating the assembly of intercalated discs (IDs) in cardiac myocytes regulated by gold nanoparticles (AuNPs) is presented. AuNPs with local nanoscale stiffness in the substrate activate β1-integrin signaling, which mediates the activation of integrin-linked kinase (ILK) and its downstream signal kinase by stimulating expression of the transcription factors GATA4 and MEF-2c.
October 10, 2016: Advanced Materials
Takayuki Kishi, Taira Mayanagi, Sadahiro Iwabuchi, Toshihide Akasaka, Kenji Sobue
The regulation of cell-substrate adhesion is tightly linked to the malignant phenotype of tumor cells and plays a role in their migration, invasion, and metastasis. Focal adhesions (FAs) are dynamic adhesion structures that anchor the cell to the extracellular matrix. Myocardin-related transcription factors (MRTFs), co-regulators of the serum response factor (SRF), regulate expression of a set of genes encoding actin cytoskeletal/FA-related proteins. Here we demonstrated that the forced expression of a constitutively active MRTF-A (CA-MRTF-A) in B16F10 melanoma cells induced the up-regulation of actin cytoskeletal and FA proteins, resulting in FA reorganization and the suppression of cell migration...
September 30, 2016: Oncotarget
Anna Skoczyńska, Elżbieta Budzisz, Kasjana Podgórna, Helena Rotsztejn
Morphology of senescent cells is constantly changing at the molecular level, which in turn leads to disruption of their function. It is connected with reduced ability to synthesize extracellular matrix (ECM) and leads to the dysfunction of integrin adhesion molecules and adhesion clusters. In skin, these factors cause a loss of communication between the extracellular matrix and fibroblasts. This contributes to the appearance of signs of aging. The aim of this study is to draw attention to the very important molecule such as paxillin, which is an adaptor protein with mass of 68 kDa...
October 6, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Shelby Calkins, Noha H Youssef
Focal adhesions (FAs) are large eukaryotic multiprotein complexes that are present in all metazoan cells and function as stable sites of tight adhesion between the extracellular matrix (ECM) and the cell's cytoskeleton. FAs consist of anchor membrane protein (integrins), scaffolding proteins (e.g. α-actinin, talin, paxillin, and vinculin), signaling proteins of the IPP complex (e.g. integrin-linked kinase, α-parvin, and PINCH), and signaling kinases (e.g. focal adhesion kinase (FAK) and Src kinase). While genes encoding complete focal adhesion machineries are present in genomes of all multicellular Metazoa; incomplete machineries were identified in the genomes of multiple non-metazoan unicellular Holozoa, basal fungal lineages, and amoebozoan representatives...
2016: PloS One
Dorota Gil, Dorota Ciołczyk-Wierzbicka, Joanna Dulińska-Litewka, Piotr Laidler
Cadherin switch is specific of epithelial-mesenchymal transition (EMT) and is closely related to tumor cell invasion. However, the molecular mechanism that promotes the phenotypic changes remains unclear and elusive. We found that integrin-linked kinase (ILK) is a key factor involved in cadherin switch. The expression and activity of ILK are elevated in a variety of cancers but its mechanisms are not exactly understood. In this report, we studied the role and mechanism of ILK in EMT of human bladder cancer...
September 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Mahesh Ramalingam, Sung-Jin Kim
Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly caused by dopaminergic neuronal cell death. Human neuroblastoma SH-SY5Y cells differentiated by retinoic acid have been used to study the in vitro PD model induced by 1-methyl-4-phenyl pyridinium (MPP(+)). In this study, pretreatment of insulin inhibited MPP(+)-induced cell membrane damages, which also inhibited the Cox-2 and α-synuclein levels. In addition, MPP(+) and/or insulin enhanced the autophagy LC3. Furthermore, MPP(+)-induced neurotoxicity diminished the integrins β3, αV and induced the syndecan-1 and -3...
October 28, 2016: Neuroscience Letters
M E Mercado-Pimentel, S Igarashi, A M Dunn, M Behbahani, C Miller, C M Read, A Jacob
Activation of PKB/AKT signaling, which requires PDK1 and PDK2 function, drives Vestibular Schwannoma (VS) and meningioma growth. PDK2 function is defined as a molecule that phosphorylates AKT-Ser473. Integrin-Linked Kinase (ILK) functions as PDK2 in PKB/AKT activation in many cancers; therefore, we hypothesized that OSU-T315, a small molecule ILK inhibitor, will inhibit the ILK-PDK2 function in PKB/AKT signaling activation in VS and meningioma cell growth. OSU-T315 decreased cell viability at IC50 < 2μM in VS (HEI193) and meningioma (Ben-Men-1) cell lines, in primary cells at < 3...
2016: Austin J Med Oncol
Ernest Ho, Iordanka A Ivanova, Lina Dagnino
The formation of tight cell-cell junctions is essential in the epidermis for its barrier properties. In this tissue, keratinocytes follow a differentiation program tightly associated with their movement from the innermost basal to the outer suprabasal layers, and with changes in their cell-cell adhesion profile. Intercellular adhesion in keratinocytes is mediated through cell-cell contacts, including E-cadherin-based adherens junctions. Although the mechanisms that mediate E-cadherin delivery to the plasma membrane have been widely studied in simple epithelia, this process is less well understood in the stratified epidermis...
September 11, 2016: Biochimica et Biophysica Acta
Z Y Wang, W Zhang, J J Yang, D K Song, J X Wei, S Gao
The clinical significance of thymosin β4 (Tβ4) expression in bladder transitional cell carcinoma (BTCC) remains unclear. The present study assessed the relationship between the expression of Tβ4 protein and the clinicopathological features, as well as the prognosis of bladder cancer patients. Tβ4 protein expression in 24 normal bladder and 138 primary BTCC tissue specimens was detected by immunohistochemistry, and the association of this expression with BTCC clinicopathological features and recurrence as well as patient survival was analyzed...
September 6, 2016: Neoplasma
Zenglin Pei, Xuan Zhang, Chunxia Ji, Song-Mei Liu, Jin Wang
Ascorbate is a pro-oxidant that generates hydrogen peroxide-dependent cytotoxity in cancer cells without adversely affecting normal cells. To determine the mechanistic basis for this phenotype, we selected Burkitt lymphoma cells resistant to ascorbate (JLPR cells) and their ascorbate-sensitive parental cells (JLPS cells). Compared with JLPS cells, the increased glucose uptake in JLPR cells (with upregulated glucose transporters, increased antioxidant enzyme activity, and altered cell cycling) conferred ascorbate-induced cytotoxicity and resistance...
August 31, 2016: Oncotarget
Xiang Zhuang, Mengxin Lv, Zhenyu Zhong, Luyu Zhang, Rong Jiang, Junxia Chen
BACKGROUND: Integrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial-mesenchymal transition (EMT). Our previous experiment demonstrated that ILK siRNA inhibited the growth and induced apoptosis of bladder cancer cells as well as increased the expression of Ribonuclease inhibitor (RI), an important cytoplasmic protein with many functions. We also reported that RI overexpression inhibited ILK and phosphorylation of AKT and GSK3β...
2016: Journal of Experimental & Clinical Cancer Research: CR
Shimona Starling, Clare Jolly
: HIV-1 efficiently disseminates by cell-cell spread at intercellular contacts called virological synapses (VS), where the virus preferentially assembles and buds. Cell-cell contact triggers active polarization of organelles and viral proteins within infected cells to the contact site to support efficient VS formation and HIV-1 spread; critically, however, which cell surface protein triggers contact-induced polarization at the VS remains unclear. Additionally, the mechanism by which the HIV-1 envelope glycoprotein (Env) is recruited to the VS remains ill defined...
November 1, 2016: Journal of Virology
Hao Chen, Hao Wang, Shuai Jiang, Jiachao Xu, Lingling Wang, Limei Qiu, Linsheng Song
miRNAs are important gene regulators at post-transcriptional level and can modulate diverse biological processes, including immune response. Dozens of species-specific miRNAs have been identified in oyster Crassostrea gigas while their functions remain largely unknown. In the present study, an oyster species-specific miRNA scaffold42648_5080 was found responsive to LPS stimulation and might target a total of 31 oyster genes possibly involved in cell communication, cellular localization and cellular response to stimulus...
October 2016: Fish & Shellfish Immunology
Chang-Fang Chiu, Jing-Ru Weng, Appaso Jadhav, Chia-Yung Wu, Aaron M Sargeant, Li-Yuan Bai
T315, an integrin-linked kinase (ILK) inhibitor, has been shown to suppress the proliferation of breast cancer, stomach cancer and chronic lymphocytic leukemia cells. Here we demonstrate that T315 decreases cell viability of acute myeloid leukemia (AML) cell lines (HL-60 and THP-1) and primary leukemia cells from AML patients in a dose-responsive manner. Normal human bone marrow cells are less sensitive than leukemia cells to T315. T315 down regulates protein kinase B (Akt) and p-Akt and induces caspase activation, poly-ADP-ribose polymerase (PARP) cleavage, apoptosis and autophagy through an ILK-independent manner...
2016: International Journal of Molecular Sciences
M H Hwang, K H Cho, K J Jeong, Y-Y Park, J M Kim, S-L Yu, C G Park, G B Mills, H Y Lee
Rab coupling protein (RCP)-induced tumor cell migration has been implicated in tumor pathophysiology and patient outcomes. In the present study, we demonstrate that RCP stabilizes β1 integrin leading to increased β1 integrin levels and activation of a signaling cascade culminating in Slug induction, epithelial-to-mesenchymal transition and increased invasion. Ectopic expression of RCP induced Slug expression. Silencing β1 integrin efficiently inhibited RCP-induced Slug expression and subsequent cancer cell invasion...
August 15, 2016: Oncogene
Mei-Fong Pang, Michael J Siedlik, Siyang Han, Melody Stallings-Mann, Derek C Radisky, Celeste M Nelson
Breast tumors are stiffer and more hypoxic than nonmalignant breast tissue. Here we report that stiff and hypoxic microenvironments promote the development of breast cancer stem-like cells (CSC) through modulation of the integrin-linked kinase ILK. Depleting ILK blocked stiffness and hypoxia-dependent acquisition of CSC marker expression and behavior, whereas ectopic expression of ILK stimulated CSC development under softer or normoxic conditions. Stiff microenvironments also promoted tumor formation and metastasis in ovo, where depleting ILK significantly abrogated the tumorigenic and metastatic potential of invasive breast cancer cells...
September 15, 2016: Cancer Research
Omar Rafael Alemán, Nancy Mora, Ricarda Cortes-Vieyra, Eileen Uribe-Querol, Carlos Rosales
Neutrophils (PMNs) are the most abundant leukocytes in the blood. PMN migrates from the circulation to sites of infection where they are responsible for antimicrobial functions. PMN uses phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. Several stimuli, including bacteria, fungi, and parasites, and some pharmacological compounds, such as Phorbol 12-myristate 13-acetate (PMA), are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation...
2016: Frontiers in Immunology
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