scholarly journals Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Krishna K. Singh ◽  
Pratiek N. Matkar ◽  
Adrian Quan ◽  
Laura-Eve Mantella ◽  
Hwee Teoh ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Ras Signaling ◽  
Hippo Signaling ◽  
Bioinformatics Analyses ◽  
Lncrna Expression ◽  
The Relationship ◽  
Mrna Transcriptome

Objective. To evaluate the relationship between TGFβsignaling and endothelial lncRNA expression.Methods.Human umbilical vein endothelial cell (HUVECs) lncRNAs and mRNAs were profiled with the Arraystar Human lncRNA Expression Microarray V3.0 after 24 hours of exposure to TGFβ1 (10 ng/mL).Results. Of the 30,584 lncRNAs screened, 2,051 were significantly upregulated and 2,393 were appreciably downregulated (P<0.05) in response to TGFβ. In the same HUVEC samples, 2,148 of the 26,106 mRNAs screened were upregulated and 1,290 were downregulated. Of these 2,051 differentially expressed upregulated lncRNAs, MALAT1, which is known to be induced by TGFβin endothelial cells, was the most (~220-fold) upregulated lncRNA. Bioinformatics analyses indicated that the differentially expressed upregulated mRNAs are primarily enriched in hippo signaling, Wnt signaling, focal adhesion, neuroactive ligand-receptor interaction, and pathways in cancer. The most downregulated are notably involved in olfactory transduction, PI3-Akt signaling, Ras signaling, neuroactive ligand-receptor interaction, and apoptosis.Conclusions.This is the first lncRNA and mRNA transcriptome profile of TGFβ-mediated changes in human endothelial cells. These observations may reveal potential new targets of TGFβin endothelial cells and novel therapeutic avenues for cardiovascular disease-associated endothelial dysfunction.

scholarly journals A global profile of glucose-sensitive endothelial-expressed long non-coding RNAs

2016 ◽  
Vol 94 (9) ◽  
pp. 1007-1014 ◽  
Author(s):  
Krishna K. Singh ◽  
Laura-Eve Mantella ◽  
Yi Pan ◽  
Adrian Quan ◽  
Sandra Sabongui ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Umbilical Vein ◽  
Vascular Complications ◽  
Differentially Expressed ◽  
Bioinformatics Analyses ◽  
Glucose Levels ◽  
Elevated Glucose ◽  
Non Coding Rnas

Hyperglycemia-related endothelial dysfunction is believed to be the crux of diabetes-associated micro- and macro-vascular complications. We conducted a systematic transcriptional survey to screen for human endothelial long non-coding RNAs (lncRNAs) regulated by elevated glucose levels. lncRNAs and protein-coding transcripts from human umbilical vein endothelial cells (HUVECs) cultured under high (25 mmol/L) or normal (5 mmol/L) glucose conditions for 24 h were profiled with the Arraystar Human LncRNA Expression Microarray V3.0. Of the 30 586 lncRNAs screened, 100 were significantly upregulated and 186 appreciably downregulated (P < 0.05) in response to high-glucose exposure. In the same HUVEC samples, 133 of the 26 109 mRNAs screened were upregulated and 166 downregulated. Of these 299 differentially expressed mRNAs, 26 were significantly associated with 28 differentially expressed long intergenic non-coding RNAs (P < 0.05). Bioinformatics analyses indicated that the mRNAs most upregulated are primarily enriched in axon guidance signaling pathways; those most downregulated are notably involved in pathways targeting vascular smooth muscle cell contraction, dopaminergic signaling, ubiquitin-mediated proteolysis, and adrenergic signaling. This is the first lncRNA and mRNA transcriptome profile of high-glucose-mediated changes in human endothelial cells. These observations may prove novel insights into novel regulatory molecules and pathways of hyperglycemia-related endothelial dysfunction and, accordingly, diabetes-associated vascular disease.

Expression profile analysis of Differentially Expressed Genes in Human Coronary Artery Endothelial Cells Induced by Serum from Kawasaki Disease: A preliminary study

2020 ◽  
Author(s):  
Xue Fan ◽  
Meng Li ◽  
Min Xiao ◽  
Cong Liu ◽  
Mingguo Xu
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Kawasaki Disease ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Healthy Children ◽  
Rna Seq ◽  
Human Coronary Artery

Abstract Background: Kawasaki disease (KD) leads to coronary artery damage and the etiology of KD is unknown. The present study was designed to explore the differentially expressed genes (DEGs) in KD serum-induced human coronary artery endothelial cells (HCAECs) by RNA-sequence (RNA-seq). Methods: HCAECs were stimulated with serum (15% (v/v)), which were collected from 20 healthy children and 20 KD patients, for 24 hours. DEGs were then detected and analyzed by RNA-seq and bioinformatics analysis. Results: The expression of SMAD1, SMAD6, CD34, CXCL1, PITX2, and APLN was validated by qPCR. 102 genes, 59 up-regulated and 43 down-regulated genes, were significantly differentially expressed in KD groups. GO enrichment analysis showed that DEGs were enriched in cellular response to cytokines, cytokine-mediated signaling pathway, and regulation of immune cells migration and chemotaxis. KEGG signaling pathway analysis showed that DEGs were mainly involved in cytokine−cytokine receptor interaction, chemokine signaling pathway, and TGF−β signaling pathway. Besides, the mRNA expression levels of SMAD1, SMAD6, CD34, CXCL1, and APLN in the KD group were significantly up-regulated compared with the normal group, whilePITX2 was significantly down-regulated. Conclusion: 102 DEGs in KD serum-induced HCAECs were identified, and six new targets were proposed as potential indicators of KD.

scholarly journals Turnover of eicosanoid precursor fatty acids among phospholipid classes and subclasses of cultured human umbilical vein endothelial cells

1989 ◽  
Vol 258 (2) ◽  
pp. 427-434 ◽  
Author(s):  
H Takayama ◽  
M H Kroll ◽  
M A Gimbrone ◽  
A I Schafer
Keyword(s):  
Fatty Acids ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Ionophore A23187 ◽  
Human Umbilical Vein ◽  
Phospholipid Classes ◽  
Specific Increase ◽  
Umbilical Vein Endothelial Cells ◽  
Relationship Of ◽  
The Relationship

Using cultured human umbilical vein endothelial cells, in which phosphatidylcholine (PC) is equally pulse-labelled by various eicosanoid precursor fatty acids (EPFAs), we have studied the remodelling of EPFAs among the phospholipid classes and subclasses with and without activation, and the relationship of this remodelling process to the selective release of arachidonic acid (AA) by phospholipase A2-mediated cell stimulation. When endothelial cells are pulse-incubated with radiolabelled EPFA for 15 min, greater than 80% of cell-associated radioactivity is present in phospholipids, among which greater than 60% is found in 1,2-diacyl-sn-glycero-3-phosphocholine (diacyl PC). After removing unincorporated radioactivity, reincubation of the pulse-labelled cells for up to 6 h results in progressive decrease in EPFA-labelled diacyl PC, increase in AA- or eicosapentaenoic acid (EPA)-labelled 1-O-alk-1-enyl-2-acyl-sn-glycero-3-phosphoethanolamine (plasmalogen PE) and increase only in AA-labelled 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl PC). This redistribution of radiolabelled phospholipids is not altered by the presence of excess non-radiolabelled EPFAs. When aspirin-treated EPFA-labelled endothelial cells are stimulated with ionophore A23187, a very selective release of AA is noted in comparison with eicosatrienoate (ETA) or EPA, accompanied by an equivalent decrease in AA-labelled diacyl PC and specific increase in AA-labelled plasmalogen PE and alkyl PC. These selective changes in AA radioactivity induced by A23187 are enhanced 2-fold by pretreating the AA-labelled cells with phorbol 12-myristate 13-acetate, which by itself induces no changes. The changes in radioactivity induced by A23187 without and with phorbol ester among the released AA, the diacyl PC and the plasmalogen PE are significantly correlated with each other. These results indicate that human endothelial cells incorporate EPFAs (AA, ETA, EPA) equally into diacyl PC but selectively release AA esterified into diacyl PC with specific remodelling into plasmalogen PE and alkyl PC.

scholarly journals Comparative iTRAQ proteomics revealed proteins associated with lobed fin regeneration in Bichirs

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Suxiang Lu ◽  
Qian Xiong ◽  
Kang Du ◽  
Xiaoni Gan ◽  
Xuzhen Wang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Multiple Reaction Monitoring ◽  
Limb Regeneration ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Differentially Expressed Proteins ◽  
Absolute Quantitation ◽  
Bioinformatics Analyses ◽  
Fin Regeneration ◽  
Early Stages

Abstract Background Polypterus senegalus can fully regenerate its pectoral lobed fins, including a complex endoskeleton, with remarkable precision. However, despite the enormous potential of this species for use in medical research, its regeneration mechanisms remain largely unknown. Methods To identify the differentially expressed proteins (DEPs) during the early stages of lobed fin regeneration in P. senegalus, we performed a differential proteomic analysis using isobaric tag for relative and absolute quantitation (iTRAQ) approach based quantitative proteome from the pectoral lobed fins at 3 time points. Furthermore, we validated the changes in protein expression with multiple-reaction monitoring (MRM) analysis. Results The experiment yielded a total of 3177 proteins and 15,091 unique peptides including 1006 non-redundant (nr) DEPs. Of these, 592 were upregulated while 349 were downregulated after lobed fin amputation when compared to the original tissue. Bioinformatics analyses showed that the DEPs were mainly associated with Ribosome and RNA transport, metabolic, ECM-receptor interaction, Golgi and endoplasmic reticulum, DNA replication, and Regulation of actin cytoskeleton. Conclusions To our knowledge, this is the first proteomic research to investigate alterations in protein levels and affected pathways in bichirs’ lobe-fin/limb regeneration. In addition, our study demonstrated a highly dynamic regulation during lobed fin regeneration in P. senegalus. These results not only provide a comprehensive dataset on differentially expressed proteins during the early stages of lobe-fin/limb regeneration but also advance our understanding of the molecular mechanisms underlying lobe-fin/limb regeneration.

scholarly journals Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function

2009 ◽  
Vol 39 (2) ◽  
pp. 100-108 ◽  
Author(s):  
Hunter Wessells ◽  
Chris J. Sullivan ◽  
Yoshiaki Tsubota ◽  
Karen L. Engel ◽  
Bryan Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Barrier Function ◽  
Umbilical Vein ◽  
Transcriptional Profiling ◽  
Corpus Cavernosum ◽  
Focal Adhesions ◽  
Receptor Interaction ◽  
Molecular Features ◽  
Junction Protein

To determine specific molecular features of endothelial cells (ECs) relevant to the physiological process of penile erection we compared gene expression of human EC derived from corpus cavernosum of men with and without erectile dysfunction (HCCEC) to coronary artery (HCAEC) and umbilical vein (HUVEC) using Affymetrix GeneChip microarrays and GeneSifter software. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. A total of 190 genes/transcripts were highly expressed only in HCCEC. Gene Ontology classification indicated cavernosal enrichment in genes related to cell adhesion, extracellular matrix, pattern specification and organogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed high expression of genes relating to ECM-receptor interaction, focal adhesions, and cytokine-cytokine receptor interaction. Real-time PCR confirmed expression differences in cadherins 2 and 11, claudin 11 (CLDN11), desmoplakin, and versican. CLDN11, a component of tight junctions not previously described in ECs, was highly expressed only in HCCEC and its knockdown by siRNA significantly reduced transendothelial electrical resistance in HCCEC. Overall, cavernosal ECs exhibited a transcriptional profile encoding matrix and adhesion proteins that regulate structural and functional characteristics of blood vessels. Contribution of the tight junction protein CLDN11 to barrier function in endothelial cells is novel and may reflect hemodynamic requirements of the corpus cavernosum.

Identification of differentially expressed circular RNAs in human nasopharyngeal carcinoma

2020 ◽  
Vol 29 (4) ◽  
pp. 483-492
Author(s):  
Hanwei Wu ◽  
Yuchen Liu ◽  
Hongfang Duan ◽  
Xiaoqin Fan ◽  
Yujie Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Ras Signaling ◽  
Epstein Barr Virus Infection ◽  
Bioinformatics Analyses ◽  
Gene Map ◽  
Barr Virus ◽  
Epstein Barr

BACKGROUND: Circular RNAs (circRNAs) are endogenous RNAs that have a covalent closed cycle configuration. circRNAs have been found to be differentially expressed in many human cancers. Therefore, circRNAs may be ideal biomarkers for the diagnosis and treatment of cancer. However, we know very little about the function of circRNAs in nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the circRNA expression profiles in NPC. METHODS: We utilized high-throughput RNA sequencing (RNA-Seq) to evaluate the circRNA expression profile in NPC A total of 13,561 unique circRNA candidates were detected. Selection of aberrantly expressed circRNAs was carried out using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. We carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to identify the biological functions of differentially expressed circRNAs. Moreover, bioinformatics analyses were implemented to predict the effects between circRNAs and cancer-related microRNAs (miRNAs), and we used Cytoscape to build a cancer-related circRNA-miRNA target gene map. Finally, to verify dysregulated circRNAs, quantitative real-time PCR was utilized. RESULTS: In NPC tissues, we found that 73 circRNAs were downregulated and 59 were upregulated. The top 12 candidate circRNAs were selected from several vital NPC pathways such as the human papillomavirus and Epstein-Barr virus infection signaling pathways (hsa05165 and hsa05169, respectively), Hepatitis B (hsa05161), and the Ras signaling pathway (hsa04014). A network map of circRNA-miRNA interactions of 12 differentially expressed circRNAs was built. Hsa_circ_0007637 expression distinguished NPC tissues from paired healthy tissues and NPC cell lines (HNE1 6-10B, 5-8F, CNE-2, and so on) from a normal epithelial (NP460) cell line. CONCLUSIONS: In this study, we investigated the profiles of differentially expressed circRNAs in NPC, and our results show that hsa_circ_0007637 may be a biomarker for NPC and play a role in its development. This observation-based research identified dysregulated circRNAs in NPC, which may assist in the development of biomarkers for this disease. Further studies on the mechanisms and functions of these circRNAs may promote our understanding of NPC tumorigenesis.

Long noncoding RNA profiles of adrenocortical cancer can be used to predict recurrence

2015 ◽  
Vol 22 (1) ◽  
pp. 99-109 ◽  
Author(s):  
A R Glover ◽  
J T Zhao ◽  
J C Ip ◽  
J C Lee ◽  
B G Robinson ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Differentially Expressed ◽  
Adrenocortical Cancer ◽  
Lncrna Expression ◽  
Adrenal Tumours ◽  
Adrenal Cortical Adenoma ◽  
Group A ◽  
Low Expression ◽  
Mrna Transcriptome

Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours have been characterised by mRNA, microRNA and methylation expression signatures, but it is unknown if this extends to lncRNAs. This study describes lncRNA expression signatures in ACC, adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC) and presents lncRNAs associated with ACC recurrence to identify novel prognostic and therapeutic targets. RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. Microarray of 21 samples (ten ACCs, five ACAs and six NACs) showed distinct patterns of lncRNA expression between each group. A total of 956 lncRNAs were differentially expressed between ACC and NAC, including known carcinogenesis-related lncRNAs such as H19, GAS5, MALAT1 and PRINS (P≤0.05); 85 lncRNAs were differentially expressed between ACC and ACA (P≤0.05). Hierarchical clustering and heat mapping showed ACC samples correctly grouped compared with NAC and ACA. Sixty-six differentially expressed lncRNAs were found to be associated with ACC recurrence (P≤0.05), one of which, PRINS, was validated in a group of 20 ACCs and also found to be associated with metastatic disease on presentation. The pathogenesis of adrenal tumours extends to lncRNA dysregulation and low expression of the lncRNA PRINS is associated with ACC recurrence.

Differentially-expressed genes related to atherosclerosis in acrolein-stimulated human umbilical vein endothelial cells

2010 ◽  
Vol 4 (4) ◽  
pp. 264-271 ◽  
Author(s):  
Seung Eun Lee ◽  
Sun Hee Lee ◽  
Dong Sun Ryu ◽  
Cheung-Seog Park ◽  
Kang-Sik Park ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Differentially Expressed Genes ◽  
Umbilical Vein ◽  
Differentially Expressed ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells
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