scholarly journals Involvement of F-Actin in Chaperonin-Containing t-Complex 1 Beta Regulating Mouse Mesangial Cell Functions in a Glucose-Induction Cell Model

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Jin-Shuen Chen ◽  
Li-Chien Chang ◽  
Chia-Chao Wu ◽  
Lai-King Yeung ◽  
Yuh-Feng Lin
Keyword(s):  
Mesangial Cell ◽  
Cell Model ◽  
Cell Contraction ◽  
Small Interference Rna ◽  
Cell Functions ◽  
T Complex ◽  
Glucose Induction ◽  
And Migration ◽  
Proliferation And Migration

The aim of this study is to investigate the role of chaperonin-containing t-complex polypeptide 1 beta (CCT2) in the regulation of mouse mesangial cell (mMC) contraction, proliferation, and migration with filamentous/globular-(F/G-) actin ratio under high glucose induction. A low CCT2 mMC model induced by treatment of small interference RNA was established. Groups with and without low CCT2 induction examined in normal and high (H) glucose conditions revealed the following major results: (1) low CCT2 or H glucose showed the ability to attenuate F/G-actin ratio; (2) groups with low F/G-actin ratio all showed less cell contraction; (3) suppression of CCT2 may reduce the proliferation and migration which were originally induced by H glucose. In conclusion, CCT2 can be used as a specific regulator for mMC contraction, proliferation, and migration affected by glucose, which mechanism may involve the alteration of F-actin, particularly for cell contraction.

Abstract 517: The CYP4A-20-HETE System Regulation of Endothelial Progenitor Cell Functions that Associated with Angiogenesis

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Li Chen ◽  
Alexander Braverman ◽  
Frank Zhang ◽  
John Falck ◽  
Ali Syed Arbab ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Vascular Effects ◽  
Endothelial Progenitor ◽  
Cell Functions ◽  
And Migration ◽  
Synthase Inhibitor ◽  
Proliferation And Migration

The CYP4A-20-HETE system regulates the neovascularization process via its potent vascular effects mainly on endothelial cells and vascular smooth muscle cells. Endothelial progenitor cells (EPC) also actively participate in physiological and pathological neovascularization. Our group first reported that the CYP4A-20-HETE system is present and functional in EPC derived from human umbilical cord blood (HUCB) and that EPC also respond to exogenous 20-HETE with increased proliferation and migration. We hypothesized that the angiogenic actions of the CYP4A-20-HETE system may involve regulation of EPC functions that associated with angiogenesis. In this study, we identified CYP4A11/22 as the main 20-HETE synthases in EPC derived from HUCB by real time PCR. We also examined the effects of exogenous 20-HETE on EPC adhesion since adhesion of EPC to extracellular matrix is an important aspect of EPC homing to the sites where angiogenesis is occurring. We found that 20-HETE (1 μM) increased EPC adhesion to fibronectin and SDF-1α coating by ∼40% and ∼35%, respectively. These increases in adhesion are completely abolished in the presence of 20-hydroxy-6, 15-eicosadienoic acid (20-HEDE), a 20-HETE antagonist. We further established the mouse ischemic hindlimb model to study the effects of pharmacological inhibition of the CYP4A/F-20-HETE system using the 20-HETE synthase inhibitor Dibromo-dodecenyl-methylsulfimide (DDMS) and 20-HEDE on compensatory angiogenesis in response to ischemia. Systemic treatment of animals with 10 mg/kg/day of either DDMS or 20-HEDE inhibited hindlimb compensatory angiogenesis by more than 50% without significant effects on the blood pressure. Specific targeting of the EPC-derived CYP4A-20-HETE system needs to be performed to further dissecting the role of systemic and EPC-derived 20-HETE on angiogenic processes. These findings implicates the CYP4A-20-HETE system as a novel regulator of EPC functions that are associated with angiogenesis and suggests that it can act as both an autocrine and paracrine regulatory factor.

scholarly journals shRNA Glut-1 inhibits cell viability, apoptosis and migration of laryngeal carcinoma HEp-2 cells through regulating Beclin-1-mediated autophagy

2020 ◽  
Author(s):  
Wen-Dong Wang ◽  
Jin-Long Zhu ◽  
Shui-Hong Zhou ◽  
Jun Fan ◽  
Yang-Yang Bao
Keyword(s):  
Cell Viability ◽  
Laryngeal Carcinoma ◽  
Migration Rate ◽  
Caspase 3 ◽  
Cell Model ◽  
Beclin 1 ◽  
Glut 1 ◽  
And Migration ◽  
Proliferation And Migration

AbstractObjectiveGlut-1 is a key regulator in the process of glucose uptake. Previous studies have shown that Glut-1 affects autophagy. However, it is unclear whether there is a correlation between Glut-1 and autophagy in the progression of laryngeal carcinoma. This study was performed to investigate the role of Glut-1 in the development of laryngeal carcinoma.MethodsA stable HEp-2 cell model was constructed by Glut-1 and Beclin-1 shRNA lentiviral infection. The autophagosome was measured by transmission electron microscopy. Protein levels of LC3, ATG5, CyclinD1, Bcl-2, Caspase-3, and c-Myc were determined by Western blotting. CCK8 assay and Transwell assays were used to determine cell viability and migration rate of HEp-2 cells, respectively. Flow cytometry was performed to analyze the rate of apoptosis. Immunofluorescence was performed to determine the expression distribution of LC3.ResultsGlut-1 knockdown significantly promoted autophagosome formation by upregulating the ratio of LC3-II/LC3-I as well as the role of rapamycin (RAP) and Beclin-1 overexpression on autophagy flux in HEp-2 cells. Glut-1 inhibition also reduced the viability of HEp-2 cells followed by the decreases in expression of cyclinD1 and c-Myc. In addition, Glut-1 depletion increased the number of apoptotic HEp-2 cells accompanied by activation of caspase-3 and downregulation of Bcl-2. Glut-1 knockdown also reduced the migration rate of HEp-2 cells by promoting the expression of N-cadherin and inhibiting the expression of E-cadherin. Beclin-1 consumption significantly reversed Gult-1 knockdown-mediated autophagy activation, resulting in promotion of both proliferation and migration and inhibition of apoptosis.ConclusionsGlut-1 knockdown-induced autophagy inhibits the proliferation and migration of HEp-2 cells, and promotes apoptosis of HEp-2 cells partly by regulating autophagy.

PI-3-kinase and MAPK regulate mesangial cell proliferation and migration in response to PDGF

1997 ◽  
Vol 273 (6) ◽  
pp. F931-F938 ◽  
Author(s):  
Goutam Ghosh Choudhury ◽  
C. Karamitsos ◽  
James Hernandez ◽  
Alessandra Gentilini ◽  
John Bardgette ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Kinase Assay ◽  
Dependent Manner ◽  
Mapk Activity ◽  
And Migration ◽  
Dose Dependent ◽  
Proliferation And Migration

Proliferation and migration are important biological responses of mesangial cells to injury. Platelet-derived growth factor (PDGF) is a prime candidate to mediate these responses in glomerular disease. PDGF and its receptor (PDGFR) are upregulated in the mesangium during glomerular injury. We have recently shown that PDGF activates phosphatidylinositol 3-kinase (PI-3-kinase) in cultured mesangial cells. The role of this enzyme and other more distal signaling pathways in regulating migration and proliferation of mesangial cells has not yet been addressed. In this study, we used two inhibitors of PI-3-kinase, wortmannin (WMN) and LY-294002, to investigate the role of this enzyme in these processes. Pretreatment of mesangial cells with WMN and LY-294002 dose-dependently inhibited PDGF-induced PI-3-kinase activity assayed in antiphosphotyrosine immunoprecipitates. WMN pretreatment also inhibited the PI-3-kinase activity associated with anti-PDGFRβ immunoprecipitates prepared from mesangial cells treated with PDGF. Pretreatment of the cells with different concentrations of WMN resulted in a dose-dependent inhibition of PDGF-induced DNA synthesis. Both WMN and LY-294002 inhibited PDGF-stimulated migration of mesangial cells in a dose-dependent manner. It has recently been shown that PI-3-kinase physically interacts with Ras protein. Because Ras is an upstream regulator of the kinase cascade leading to the activation of mitogen-activated protein kinase (MAPK), we determined whether activation of PI-3-kinase is necessary for activation of MAPK. Pretreatment of mesangial cells with WMN and LY-294002 significantly inhibited PDGF-induced MAPK activity as measured by immune complex kinase assay of MAPK immunoprecipitates. Furthermore, PD-098059, an inhibitor of MAPK-activating kinase inhibited PDGF-induced MAPK activity and resulted in significant reduction of mesangial cell migration in response to PDGF. These data indicate that MAPK is a downstream target of PI-3-kinase and that both these enzymes are involved in regulating proliferation and migration of mesangial cells.

scholarly journals Expression and Role of the Intermediate-Conductance Calcium-Activated Potassium Channel KCa3.1 in Glioblastoma

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Luigi Catacuzzeno ◽  
Bernard Fioretti ◽  
Fabio Franciolini
Keyword(s):  
Normal Brain ◽  
Glioblastoma Cells ◽  
Altered Expression ◽  
Functional Roles ◽  
Cell Functions ◽  
And Migration ◽  
And Function ◽  
Calcium Activated Potassium Channel ◽  
Proliferation And Migration

Glioblastomas are characterized by altered expression of several ion channels that have important consequences in cell functions associated with their aggressiveness, such as cell survival, proliferation, and migration. Data on the altered expression and function of the intermediate-conductance calcium-activated K (KCa3.1) channels in glioblastoma cells have only recently become available. This paper aims to (i) illustrate the main structural, biophysical, pharmacological, and modulatory properties of the KCa3.1 channel, (ii) provide a detailed account of data on the expression of this channel in glioblastoma cells, as compared to normal brain tissue, and (iii) critically discuss its major functional roles. Available data suggest that KCa3.1 channels (i) are highly expressed in glioblastoma cells but only scantly in the normal brain parenchima, (ii) play an important role in the control of glioblastoma cell migration. Altogether, these data suggest KCa3.1 channels as potential candidates for a targeted therapy against this tumor.

Role of microenvironment on proliferation and migration of an SDHB silenced murine Pheochromocytoma cell line

2017 ◽  
Author(s):  
Serena Martinelli ◽  
Vanessa D'Antongiovanni ◽  
Susan Richter ◽  
Letizia Canu ◽  
Tonino Ercolino ◽  
...  
Keyword(s):  
Cell Line ◽  
Pheochromocytoma Cell ◽  
And Migration ◽  
Proliferation And Migration

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Direct Target ◽  
And Migration ◽  
High Level ◽  
Cxcr5 Expression ◽  
Proliferation And Migration

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

scholarly journals miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease

2018 ◽  
Vol 48 (4) ◽  
pp. 1804-1814 ◽  
Author(s):  
Xing Rong ◽  
Donghui Ge ◽  
Danping Shen ◽  
Xianda Chen ◽  
Xuliang Wang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Kawasaki Disease ◽  
Therapeutic Target ◽  
Umbilical Vein ◽  
Luciferase Reporter ◽  
Endothelial Cell Proliferation ◽  
Cell Functions ◽  
Potential Biomarker ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment.

FAM196B promotes proliferation and migration via regulating epithelial-mesenchymal transition in esophageal cancer

2021 ◽  
pp. 1-8
Author(s):  
Haifeng Xia ◽  
Fang Hu ◽  
Liangbin Pan ◽  
Chengcheng Xu ◽  
Haitao Huang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Western Blot ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Ec Cells ◽  
And Migration ◽  
Proliferation And Migration

BACKGROUND: EC (esophageal cancer) is a common cancer among people in the world. The molecular mechanism of FAM196B (family with sequence similarity 196 member B) in EC is still unclear. This article aimed to clarify the role of FAM196B in EC. METHODS: The expression of FAM196B in EC tissues was detected using qRT-PCR. The prognosis of FAM196B in EC patients was determined by log-rank kaplan-Meier survival analysis and Cox regression analysis. Furthermore, shRNA was used to knockdown the expression of FAM196B in EC cell lines. MTT, wound healing assays and western blot were used to determine the role of FAM196B in EC cells. RESULTS: In our research, we found that the expression of FAM196B was up-regulated in EC tissues. The increased expression of FAM196B was significantly correlated with differentiation, lymph node metastasis, stage, and poor survival. The proliferation and migration of EC cells were inhibited after FAM196B-shRNA transfection in vitro and vivo. The western blot result showed that FAM196B could regulate EMT. CONCLUSION: These results suggested that FAM196B severs as an oncogene and promotes cell proliferation and migration in EC. In addition, FAM196B may be a potential therapeutic target for EC patients.

scholarly journals Paradoxical role of high mobility group box 1 in glioma: a suppressor or a promoter?

2017 ◽  
Author(s):  
Richard A. Seidu ◽  
Min Wu ◽  
Zhaoliang Su ◽  
Huaxi Xu
Keyword(s):  
Molecular Mechanisms ◽  
High Mobility ◽  
Treatment Resistance ◽  
High Mobility Group ◽  
Tissue Invasion ◽  
Self Sufficiency ◽  
Glycation End Products ◽  
And Migration ◽  
Proliferation And Migration

Gliomas represent 60% of primary intracranial brain tumors and 80% of all malignant types, with highest morbidity and mortality worldwide. Although glioma has been extensively studied, the molecular mechanisms underlying its pathology remain poorly understood. Clarification of the molecular mechanisms involved in their development and/or treatment resistance is highly required. High mobility group box 1 protein (HMGB1) is a nuclear protein that can also act as an extracellular trigger of inflammation, proliferation and migration, through receptor for advanced glycation end products and toll like receptors in a number of cancers including gliomas. It is known that excessive release of HMGB1 in cancer leads to unlimited replicative potential, ability to develop blood vessels (angiogenesis), evasion of programmed cell death (apoptosis), self-sufficiency in growth signals, insensitivity to inhibitors of growth, inflammation, tissue invasion and metastasis. In this review we explore the mechanisms by which HMGB1 regulates apoptosis and autophagy in glioma. We also looked at how HMGB1 mediates glioma regression and promotes angiogenesis as well as possible signaling pathways with an attempt to provide potential therapeutic targets for the treatment of glioma.

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