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Integrin linked kinase

YingHui Zhang, Bing Wang, Feng Guo, ZhiZhen Li, GuiJun Qin
Diabetic nephropathy is one of the manifestations of systemic microangiopathy in diabetes. Hesperetin, a natural flavanone glycoside compound in citrus fruits, has been demonstrated to exert hypoglycemic effects and protect kidney in experimental diabetic animals. The current study was aimed to investigate the mechanisms underlying the hypoglycemic effects of hesperetin in high-fat/streptozocin (STZ)-induced diabetic nephropathy. The results showed that mice in whom hesperetin was administered for 4 weeks attenuated the increased fasting blood glucose and impaired glucose tolerance ability that was observed in high-fat/STZ mice...
June 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mohammed Alasseiri, Afsar U Ahmed, Bryan R G Williams
Integrin-linked kinase (ILK) has emerged as a critical adaptor and mediator protein in cell signaling pathways that is commonly deregulated in acute myeloid leukemia (AML). This has led to the expectation that therapeutic targeting of ILK may be a useful option in treating leukemia. Although ILK can regulate many cellular processes, including cell differentiation, survival, migration, apoptosis and production of pro-inflammatory cytokines, its role in promoting AML is still unclear. However, its ability to mediate phosphorylation and regulate the important hematopoietic stem cell regulators protein kinase B (AKT) and glycogen synthase kinase-3β supports ILK as an attractive target for the development of novel anticancer therapeutics...
June 7, 2018: Cytokine & Growth Factor Reviews
Alicia M Salvi, Kris A DeMali
Throughout their lifetimes, all cells experience force. These forces are sensed by cell surface adhesion receptors, such as the cadherins and integrins. Much attention has focused on identifying how these adhesion receptors transmit force. In contrast, less is known regarding how these force-activated pathways are integrated with other cellular processes. In this review, we describe how cadherins and integrins transmit force, and discuss how these adhesion receptors are linked to cell metabolism. We focus on understanding this connection by highlighting how the cadherins and integrins interact with a master regulator of energy homeostasis, AMP-activated protein kinase (AMPK) and its upstream activator, Liver Kinase B1 (LKB1)...
June 11, 2018: Current Opinion in Cell Biology
Suisui Hao, Yu Zhang, Jie Meng, Jian Liu, Tao Wen, Ning Gu, Haiyan Xu
Most of the existing scaffolds for guiding tissue regeneration do not provide direct mechanical stimulation to the cells grown on them. In this work, we used nanofibrous superparamagnetic scaffolds with applied magnetic fields to build a "dynamic" scaffold platform and investigated the modulating effects of this platform on the phenotypes of fibroblasts. The results of enzyme-linked immunosorbent and transwell assays indicated that fibroblasts cultivated in this platform secreted significantly higher type I collagen, vascular endothelial growth factor A, and transforming growth factor-β1 and did so in a time-dependent manner...
June 14, 2018: ACS Applied Materials & Interfaces
Josef Köhrle
More than a century after the discovery of L-Thyroxine, the main thyroid hormone secreted solely by the thyroid gland, several metabolites of this iodinated, tyrosine-derived ancestral hormone have been identified. These are utilized as hormones during development, differentiation, metamorphosis, and regulation of most biochemical reactions in vertebrates and their precursor species. Among those metabolites are the thyromimetically active 3,3',5-Triiodo-L-thyronine (T3) and 3,5-Diiodo-L-thronine, reverse-T3 (3,3',5'-Triiodo-L-thyronine) with still unclear function, the recently re-discovered thyronamines (e...
2018: Methods in Molecular Biology
Sunayana Begum Syed, Faez Iqbal Khan, Sabab Hasan Khan, Saurabha Srivastava, Gulam Mustafa Hasan, Kevin A Lobb, Asimul Islam, Md Imtaiyaz Hassan, Faizan Ahmad
Integrin-linked kinase (ILK) is a ubiquitously expressed Ser/Thr kinase which plays significant role in the cell-matrix interactions and growth factor signalling. In this study, guanidinium chloride (GdmCl)-induced unfolding of kinase domain of ILK (ILK193-446 ) was carried out at pH 7.5 and 25 °C. Eventually, denaturation curves of mean residue ellipticity at 222 nm ([θ]222 ) and fluorescence emission spectrum were analysed to estimate stability parameters. The optical properties maximum emission (λmax ) and difference absorption coefficient at 292 nm (Δε292 ) were analysed...
June 6, 2018: International Journal of Biological Macromolecules
Banghua Zhong, Kewei Wang, Hao Xu, Fanmin Kong
Background: Formin-like 2 (FMNL2) is a member of Formin family which governs cytokinesis, cellular polarity and morphogenesis. Dysregulation of FMNL2 has been discovered in cancers and is closely related to cancers. However, the role of FMNL2 in gastric cancer remains unclear. In this study, we aimed to investigate the role of FMNL2 in gastric cancer cells. Methods: A FMNL2-specific shRNA was employed to decrease the endogenous expression of FMNL2. Then the degree of proliferation, apoptosis, migration and invasion of gastric cancer cells was assessed by MTT assay, flow cytometry, wound healing assay and transwell assay, respectively...
2018: Cancer Cell International
Huawei Wang, John Lapek, Ken Fujimura, Jan Strnadel, Bei Liu, David J Gonzalez, Wei Zhang, Felicia Watson, Vicky Yu, Chao Liu, Carina Muccilo Melo, Yury I Miller, Kathryn C Elliott, David A Cheresh, Richard L Klemke
PEAK1 is a newly described tyrosine kinase and scaffold protein that transmits integrin-mediated extracellular matrix (ECM) signals to facilitate cell movement and growth. While aberrant expression of PEAK1 has been linked to cancer progression, its normal physiological role in vertebrate biology is not known. Here we provide evidence that PEAK1 plays a central role in orchestrating new vessel formation in vertebrates. Deletion of the PEAK1 gene in zebrafish, mice, and human endothelial cells (ECs) induced severe defects in new blood vessel formation due to deficiencies in EC proliferation, survival, and migration...
2018: Cell Discovery
Wenlong Liu, Qingxiang Zeng, Lifeng Zhou, Yan Li, Yanqiu Chen, RenZhong Luo
BACKGROUND: Recent studies suggest that T helper 17 (Th17) cell subset, a distinct pro-inflammatory CD4+ T cell lineage, may play an important role in the pathophysiology of allergic rhinitis (AR). However, the regulation of Th17 response in allergic disease is not well characterized. METHODS: Thirty AR and 30 healthy children were enrolled. Serum leptin and OPN levels were measured and their correlation with IL-17 expression was analyzed using enzyme-linked immunosorbnent assay (ELISA)...
May 28, 2018: Pediatric Allergy and Immunology
Fen Xu, Xiaoyan Zhou, Jian Hao, Hua Dai, Jian Zhang, Yuanqiao He, Hua Hao
Epithelial-mesenchymal Transition (EMT) and migration play an important role in tumor progression, and lipoxin (LX), the 'stop signal' for inflammation, has been studied in basic research for its anti-inflammatory or inflammatory pro-resolving properties. Here, in the in vitro experiment, we showed that LXA4 could inhibit the EMT and migration in phorbol myristate acetate (PMA) or activated conditioned medium (ACM)-stimulated Hep3B cells by downregulation of integrin-linked kinase (ILK), a pseudokinase in cytoplasm and these effects were via inhibiting the phosphorylation of Akt and GSK3β...
May 19, 2018: Prostaglandins & Other Lipid Mediators
Xu-Feng Xu, You-Cui Wang, Liang Zong, Zhe-Yu Chen, Yan Li
Alterations in adult neurogenesis have been regarded as a major cause of cognitive impairment in Alzheimer's disease (AD). The underlying mechanism of neurogenesis deficiency in AD remains unclear. In this study, we reported that Integrin-linked Kinase (ILK) protein levels and phosphorylation were significantly decreased in the hippocampus of APP/PS1 mice. Increased ILK expression of dentate gyrus (DG) rescued the hippocampus-dependent neurogenesis and memory deficits in APP/PS1 mice. Moreover, we demonstrated that the effect of ILK overexpression in the hippocampus was exerted via AKT-GSK3β pathway...
May 19, 2018: Brain Research
Takuya Kuwashiro, Shinji Iwane, Xia Jinghe, Sachiko Matsuhashi, Yuichiro Eguchi, Keizo Anzai, Kazuma Fujimoto, Toshihiko Mizuta, Naoya Sakamoto, Masanori Ikeda, Nobuyuki Kato, Iwata Ozaki
Although interferon (IFN)‑based treatment of patients with chronic hepatitis C virus (HCV) infection is widely applied, treatment resistance is often observed in patients with advanced liver fibrosis. Given that the molecular mechanisms of IFN resistance in liver fibrosis remain elusive, the present study investigated the effects of extracellular matrix (ECM) on IFN signaling in hepatic cells. The native HuH‑7 human hepatoma cell line and HuH‑7 cells were stably transfected with full‑length HCV‑RNA fused with Renilla luciferase (OR6 cells) were cultured on ECM‑coated dishes or non‑coated plastic dishes (NDs), and treated with human IFN‑α...
May 18, 2018: International Journal of Molecular Medicine
Michael Hartmut Feige, Olga Sokolova, Anna Pickenhahn, Gunter Maubach, Michael Naumann
Helicobacter pylori infection persists in more than half of the world's population and represents a risk factor for peptic ulcer disease and gastric cancer. Virulent strains of H. pylori carry a cag pathogenicity island (cagPAI), which encodes a type IV secretion system (T4SS) with the capability to inject the effector protein cytotoxin-associated gene A (CagA) into eukaryotic cells. Colonisation of the gastric epithelium by H. pylori provokes direct activation of the proinflammatory and survival factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)...
May 14, 2018: International Journal of Medical Microbiology: IJMM
Tielong Liu, Yonggang Liu, Jiashi Cao, Xin Gao, Jing Wang, Guanghui Chen, Yang Wang, Ge Liu, Guangjian Bai, Yiwei Hu, Jiaxiang Yang, Lianfeng Dong, Xinbao Quan, Weiwei Zou
BACKGROUND/AIMS: Integrin-linked kinase-associated phosphatase (ILKAP), a serine/threonine phosphatase that belongs to the protein phosphatase 2C family, has a role in cell survival and apoptosis. Hypoxia-inducible factor 1α (HIF-1α) is the key transcription factor in the response to oxygen deficiency in mammals. Direct phosphorylation and dephosphorylation of HIF-1α affect its function. The present study investigated the role of ILKAP on HIF-1α dephosphorylation and cell behavior...
May 5, 2018: Cellular Physiology and Biochemistry
Norihisa Saeki, Akira Saito, Yuki Sugaya, Mitsuhiro Amemiya, Hiroe Ono, Rie Komatsuzaki, Kazuyoshi Yanagihara, Hiroki Sasaki
BACKGROUND/AIM: Overall survival for the high-risk group of neuroblastoma (NB) remains at 40-50%. An integrative genomics study revealed that LIM domain only 1 (LMO1) encoding a transcriptional regulator to be an NB-susceptibility gene with a tumor-promoting activity, that needs to be revealed. MATERIALS AND METHODS: We conducted chromatin immunoprecipitation and DNA sequencing analyses and cell proliferation assays on two NB cell lines. RESULTS: We identified three genes regulated by LMO1 in the cells, LIM and senescent cell antigen-like domains 1 (LIMS1), Ras suppressor protein 1 (RSU1) and relaxin 2 (RLN2)...
May 2018: Cancer Genomics & Proteomics
Alexander T Hardy, Verónica Palma-Barqueros, Stephanie K Watson, Jean-Daniel Malcor, Johannes A Eble, Elizabeth E Gardiner, José E Blanco, Rafael Guijarro-Campillo, Juan L Delgado, María L Lozano, Raúl Teruel-Montoya, Vicente Vicente, Steve P Watson, José Rivera, Francisca Ferrer-Marín
Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2β1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation...
June 2018: Thrombosis and Haemostasis
Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu
BACKGROUND: The inhibitory receptor programmed cell death protein 1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic viral infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine the effect of PD-1 signaling on NK cells...
April 18, 2018: Journal of Allergy and Clinical Immunology
Xiaoying Zhang, Yinhui Xu, Hongbo Liu, Pan Zhao, Yafang Chen, Zhijie Yue, Zhiqing Zhang, Xiaofang Wang
Mesenchymal stromal cells are proven to be likely induce the angiogenic response in multiple myeloma and thus represent an enticing target for antiangiogenesis therapies for multiple myeloma. Substantial evidence indicates that angiogenesis in multiple myeloma is complex and involves direct production of angiogenic cytokines by abnormal plasma cells and these B-cell neoplasia generated pathophysiology change within the microenvironment. In this study, we demonstrated that mesenchymal stromal cells cultured with U266/Lp-1 under hypoxic conditions resulted in an increased α-smooth muscle actin expression and high productive levels of both hypoxia-inducible factor-2α and integrin-linked kinase proteins...
January 1, 2018: Technology in Cancer Research & Treatment
Sushma Bartaula-Brevik, Marte Karen Lindstad Brattås, Tor Henrik Anderson Tvedt, Håkon Reikvam, Øystein Bruserud
Splenic tyrosine kinase (SYK) is a non-receptor tyrosine kinase. It is important for downstream signaling from several cell surface receptors, including Fc receptors, complement receptors and integrins. SYK can have either oncogenic or tumor suppressor activity in human malignancies. Recent studies suggest that SYK inhibition may have an antileukemic effect in human acute myeloid leukemia (AML). Areas covered: Relevant publications were identified through literature searches in the PubMed database. We searched for (i) original articles describing the results from clinical studies of SYK inhibition; (ii) published articles describing the importance of SYK in human malignancies, especially AML...
April 2018: Expert Opinion on Investigational Drugs
Xiu-Mei Yang, Chun-Guang Duan, Jian Zhang, Xiao-Jie Qu, Yu-Sheng Wang
Purpose: Vasculogenesis has been shown to contribute to the formation of choroidal neovascularization (CNV). However, the mechanism behind the recruitment of endothelial progenitor cells (EPC) to CNV is not well understood. Therefore, we were interested to know whether integrin-linked kinase (ILK) plays a role in recruiting EPC to CNV, and its possible mechanism. Methods: We investigated the effect of hypoxia on retinal pigment epithelium (RPE) cells expressing ILK, hypoxia-inducible factor 1α (HIF-1α), stromal-derived factor-1 (SDF-1), and vascular endothelial growth factor (VEGF), and we further examined the effect of ILK small interfering RNA (siRNA) on their expression...
April 1, 2018: Investigative Ophthalmology & Visual Science
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