scholarly journals Effects of icariin on long noncoding RNA and mRNA expression profile in the aortas of apoE-deficient mice

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Yibing Zhang ◽  
Rui Xu ◽  
Xiangjun Li ◽  
Qi Tan ◽  
Peng Huang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
High Fat Diet ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Protective Mechanism ◽  
Beneficial Effects ◽  
Plaque Area ◽  
Kinase C ◽  
Global Signal ◽  
Deficient Mice

Abstract Objective : The beneficial effects of icariin (ICA) in ameliorating atherosclerosis (AS) are well known, but the underlying protective mechanism has not been fully elucidated. The present study aimed to investigate altered long noncosing RNA (lncRNA) and mRNA expression profiles in ApoE−/− mice after ICA treatment. Method : The atherosclerotic plaque area was evaluated on high-fat diet (HFD)-induced ApoE−/− mice treated with either ICA or vehicle. LncRNA and mRNA integrated microarrays was performed on aortic tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were utilized to explore the significant function and pathway of the differentially expressed (DE) mRNAs, global signal transduction network were constructed to select key mRNAs, and lncRNA–mRNA co-expression network was built to find out the interactions between lncRNA and mRNA. Quantitative real-time PCR (qPCR) was used to further validate the expressions of selected lncRNAs and mRNAs. Results : Administration of ICA significantly reduced plaque size after 12 weeks (P<0.05). A total of 1512 DE lncRNAs and 2059 DE mRNAs were identified. The mRNAs: protein kinase C, β (Prkcb), Cyp2c65, Mapk10, Calmodulin 5 (Calm5), Calmodulin-like 3 (Calml3) and Camk4 were selected as hub mRNAs, the correlated lncRNAs in co-expression network were identified as important regulatory lncRNAs. The identified target pairs such as lncRNA-NONMMUT000659/Prkcb may play critical roles in AS development mediated by ICA. Conclusion : Taken together, our study highlights a panel of DE lncRNAs and mRNAs that could explain the molecular mechanism of ICA’s anti-atherosclerotic effects. The work lays a foundation for subsequent genes functional researches, which could contribute to provide new therapeutic targets for AS.

scholarly journals Effects of Interleukin-1β on Long Noncoding RNA and mRNA Expression Profiles of Human Synovial Fluid-derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Yang-peng Sun ◽  
Yun-yang Lu ◽  
Jianyu Chen ◽  
Jia-hao Bao ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Synovial Fluid ◽  
Mrna Expression ◽  
Temporomandibular Joint ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Biological Behavior ◽  
Antisense Lncrnas

Abstract Synovial fluid-derived mesenchymal stem cells (SFMSCs) play important regulatory roles in the physiological balance of the temporomandibular joint. Interleukin (IL)-1β regulates the biological behavior of SFMSCs; however, the effects of IL-1β on long noncoding RNA (lncRNA) and mRNA expression in SFMSCs in the temporomandibular joint are unclear. Here, we evaluated the lncRNA and mRNA expression profiles of IL-1β-stimulated SFMSCs. Using microarrays, we identified 286 lncRNAs (222 upregulated, 64 downregulated) and 304 mRNAs (242 upregulated, 62 downregulated) that were differentially expressed after treatment with IL-1β (fold change ≥ 2, P < 0.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis found that one of the most significantly enriched pathways was the NF-κB pathway. Five paired antisense lncRNAs and mRNAs, eight paired enhancer lncRNAs and mRNAs, and nine paired long intergenic noncoding RNAs and mRNAs were predicted to be co-expressed. A network constructed by the top 30 k-score genes was visualized and evaluated. We found a co-expression relationship between ENST00000427824 and ENST00000307407 and between LOC541472 and IL6, which are related to NF-κB pathway activation. Overall, our results provide important insights into changes in lncRNA and mRNA expression in IL-1β-stimulated SFMSCs, which can facilitate the identification of potential therapeutic targets.

Long noncoding RNA‐mRNA expression profiles and validation in pancreatic neuroendocrine neoplasms

2020 ◽  
Vol 92 (4) ◽  
pp. 312-322 ◽  
Author(s):  
Meng Ji ◽  
Liang Tang ◽  
Rumei Ding ◽  
Ligang Shi ◽  
Anan Liu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Neuroendocrine Neoplasms ◽  
Pancreatic Neuroendocrine Neoplasms

A High Through-Put Screen Identifies MCP-1 (CCL2) As a Novel Regulator of Iron Homeostasis and a Modifier of Hereditary Hemochromatosis Disease Severity

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 685-685
Author(s):  
Martina U. Muckenthaler ◽  
Maja Vujic Spasic ◽  
Katarzyna Mleczko-Sanecka ◽  
Mingang Zhu ◽  
Rainer Pepperkok ◽  
...  
Keyword(s):  
Iron Overload ◽  
Mrna Expression ◽  
Disease Severity ◽  
Iron Homeostasis ◽  
Expression Profiles ◽  
Hereditary Hemochromatosis ◽  
Transferrin Saturation ◽  
Human Cells ◽  
Liver Iron ◽  
Deficient Mice

Abstract Abstract 685 To identify genes that modify the severity of human iron disorders we pre-selected 74 genes from gene expression profiles of cells and tissues with altered iron levels and assessed whether siRNA-mediated knock-down of these genes affects uptake of transferrin, a key cellular process to acquire iron. This screen identifies the monocyte chemoattractant protein-1 (MCP-1), also known as CCL2, as a critical suppressor of transferrin receptor mRNA expression in human cells. We next analyzed CCL2-deficient mice and demonstrate profound alterations of parameters of systemic iron homeostasis. Specifically, CCL2 knock-out mice show decreased serum iron levels and transferrin saturation, strong iron-overload in the spleen and duodenum as well as mild iron accumulation in the liver. Iron imbalance in CCL2−/− mice is unlikely explained by an impairment of the major control system of systemic iron homeostasis, the hepcidin/ferroportin regulatory system: hepcidin mRNA expression is unaltered and splenic ferroportin protein expression is strongly increased in CCL2−/− mice, as would be expected as a consequence of splenic iron overload. We speculate that increased iron absorption from the plasma, possibly mediated by inappropriately high levels of TfR1 in the spleen, duodenum and liver, may be responsible for tissue iron overload. It is of note that CCL2 levels are strongly decreased in Hfe-deficient mice and patients with Hfe-associated Hereditary Hemochromatosis (HH). We therefore asked whether CCL2 levels could modify disease severity of HH. Analysis of 51 HH patients, all homozygous for the C282Y HFE mutation, confirms significantly lower MCP-1 levels in the serum compared to a group of 23 sex- and age-matched normal controls. Importantly, CCL2 levels in HH patients show a significant negative correlation with liver iron overload at the time point of diagnosis. Furthermore, low CCL2 concentrations are significantly associated with the HLA-A3 genotype and the CD8+ T lymphocyte phenotype, both traits previously shown to correlate with iron overload in HH patients. These patient data and the data from CCL2-deficient mice suggest that appropriate CCL2 expression is required to prevent iron overload. Taken together our data demonstrate the power of siRNA screens to identify novel regulators of iron metabolism in human cells that are critically involved in maintaining systemic iron homeostasis in the mouse and that play a role in modifying hepatic iron overload in the frequent iron overload disorder Hereditary Hemochromatosis. Disclosures: No relevant conflicts of interest to declare.

LncRNA-mRNA Expression Profiles and Functional Networks Associated with Cognitive Impairment in Folate-deficient Mice

2021 ◽  
Vol 24 ◽  
Author(s):  
Xiaojin Feng ◽  
Fenfang Zhan ◽  
Jialing Hu ◽  
Fuzhou Hua ◽  
Guohai Xu
Keyword(s):  
Gene Expression ◽  
Cognitive Impairment ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Functional Networks ◽  
Ppi Network ◽  
Hub Genes ◽  
Cerna Network ◽  
Deficient Mice

Background: Cognitive impairment is a common neurocognitive disorder that affects millions of worldwide people’s health,related tofolate deficiency. Objective: The present study aimed to investigate the lncRNA-mRNA functional networks associated with cognitive impairment in folate-deficient mice and elucidate their possible molecular mechanisms. Methods: We downloaded the gene expression profile (GSE148126) of lncRNAs and mRNAs from NCBI Gene Expression Omnibus (GEO) database. Four groups of mouse hippocampi were analyzed, including 4 months (4mo) and 18 months (18mo) of folic acid (FA) deficiency/supplementation. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified using gplots and heatmap packages. The functions of the DEmRNAs were evaluated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The hub genes wereidentified by CytoHubba plugins of Cytoscape, and protein-protein interaction (PPI) network of deregulated mRNAs was performed using STRING database. Finally, lncRNA-mRNA co-expression and competitive endogenous RNA (ceRNA) network analyses were constructed. Results: In total, we screened 67 lncRNAs with 211 mRNAs, and 89 lncRNAs with 229 mRNAs were differentially expressed in 4mo_FAand 18mo_FA deficient mice, respectively. GO analyses indicated that DEmRNAs were highly related to terms involved in binding and biological regulation. KEGG pathway analyses demonstrated that these genes were significantly enriched for Renin secretion, Pancreatic secretion and AMPK signaling pathways in 18mo_FA deficiency group. Subsequently, the top 5 hub genes werescreened from the PPI network, which may be key genes with the progression of folate deficiency. Upon the lncRNA-mRNA co-expression network analysis, we identified the top 10 lncRNAs having the maximum number of connections with related mRNAs. Finally, a ceRNA network was constructed for DE lncRNAs and DEmRNAs, and several pivotal miRNAs were predicted. Conclusions: This study identified the lncRNA-mRNA expression profiles and functional networks associated with cognitive impairment in folate-deficient mice, which provided support for the possible mechanisms and therapy for this disease.

scholarly journals Comparison of Long Noncoding RNA and mRNA Expression Profiles in Mesenchymal Stem Cells Derived from Human Periodontal Ligament and Bone Marrow

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Rui Dong ◽  
Juan Du ◽  
Liping Wang ◽  
Jinsong Wang ◽  
Gang Ding ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mrna Expression ◽  
Periodontal Ligament ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Expression Profiles ◽  
Wnt Signaling Pathway

Mesenchymal stem cells (MSCs) in different anatomic locations possess diverse biological activities. Maintaining the pluripotent state and differentiation depend on the expression and regulation of thousands of genes, but it remains unclear which molecular mechanisms underlie MSC diversity. Thus, potential MSC applications are restricted. Long noncoding RNAs (lncRNAs) are implicated in the complex molecular circuitry of cellular processes. We investigated differences in lncRNA and mRNA expression profiles between bone marrow stem cells (BMSCs) and periodontal ligament stem cells (PDLSCs) with lncRNA microarray assays and bioinformatics analysis. In PDLSCs, numerous lncRNAs were significantly upregulated (n=457) or downregulated (n=513) compared to BMSCs. Furthermore, 1,578 mRNAs were differentially expressed. These genes implicated cellular pathways that may be associated with MSC characteristics, including apoptosis, MAPK, cell cycle, and Wnt signaling pathway. Signal-net analysis indicated that phospholipase C beta 4, filamin B beta, calcium/calmodulin-dependent protein kinase II gamma, and the ionotropic glutamate receptor, AMPA 1, had the highest betweenness centrality among significant genes in the differential gene profile network. A comparison between the coding-noncoding gene coexpression networks of PDLSCs and BMSCs identified chemokine (C-X-C motif) ligand 12 as a core regulatory factor in MSC biology. These results provided insight into the mechanisms underlying MSC biology.

scholarly journals Proanthocyanidin Attenuation of Oxidative Stress and NF-κB Protects Apolipoprotein E-Deficient Mice against Diabetic Nephropathy

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Abdulrahman L. Al-Malki ◽  
Ahmed Amir Radwan Sayed ◽  
Haddad A. El Rabey
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Apolipoprotein E ◽  
High Fat Diet ◽  
Diabetic Mice ◽  
High Cholesterol ◽  
Beneficial Effects ◽  
Cholesterol Levels ◽  
Reduced Activity ◽  
Deficient Mice

Hyperlipidemia and hyperglycemia result in oxidative stress and play a major role in the development of diabetic nephropathy (DN). We explored the effects of proanthocyanidin (PA) on the induction and progression of DN in apolipoprotein E-deficient mice. Diabetes Mellitus was induced in ten-week-old male apoE−/−mice using streptozotocin (STZ). Mice were fed with a high-fat diet in presence or absence of PA. PA treatment significantly reduced the high cholesterol levels, restored renal functions, and reduced albuminuria in the PA-treated diabetic mice compared with the diabetic untreated mice. In addition, the glomerular mesangial expansion in the diabetic mice was attenuated as a result of PA supplementation. Moreover, PA treatment restored the elevated levels of MDA and CML and the reduced activity of SOD and GSH in the diabetic mice. Furthermore, PA feeding reduced the activation and translocation of NF-κB to the nucleus compared with the diabetic untreated animals. Reduction of NF-κB activation resulted in the attenuation of the expression of IL-6, TGFβ, and RAGE which protected PA-treated mice against DN. The renoprotective effects of PA were found to be time independent regardless of whether the dietary feeding with PA was started pre-, co-, or post-STZ injection. In conclusion, part of the beneficial effects of PA includes the disruption of the detrimental AGE-RAGE-NFκB pathways.

scholarly journals NLRP3 inflammasome deficiency attenuates metabolic disturbances involving alterations in the gut microbial profile in mice exposed to high fat diet

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marina Sokolova ◽  
Kuan Yang ◽  
Simen H. Hansen ◽  
Mieke C. Louwe ◽  
Martin Kummen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Plasma Metabolites ◽  
Inflammasome Activation ◽  
Microbiota Composition ◽  
High Fat ◽  
Beneficial Effects ◽  
Deficient Mice ◽  
Gut Microbiota Composition

AbstractObesity-related diseases (e.g. type 2 diabetes mellitus and cardiovascular disorders) represent an increasing health problem worldwide. NLRP3 inflammasome activation may underlie obesity-induced inflammation and insulin resistance, and NLRP3 deficient mice exposed to high fat diet (HFD) appear to be protected from left ventricle (LV) concentric remodeling. Herein, we investigated if these beneficial effects were associated with alterations in plasma metabolites, using metabolomic and lipidomic analysis, and gut microbiota composition, using 16S rRNA sequencing of cecum content, comparing NLRP3 deficient and wild type (WT) mice on HFD and control diet. Obese NLRP3 deficient mice had lower systemic ceramide levels, potentially resulting attenuating inflammation, altered hepatic expression of fatty acids (FA) with lower mono-saturated FA and higher polyunsaturated FA levels, potentially counteracting development of liver steatosis, downregulated myocardial energy metabolism as assessed by proteomic analyses of LV heart tissue, and different levels of bile acids as compared with WT mice. These changes were accompanied by an altered composition of gut microbiota associated with decreased systemic levels of tri-methylamine-N-oxide and lipopolysaccharide, potentially inducing attenuating systemic inflammation and beneficial effects on lipid metabolism. Our findings support a role of NLRP3 inflammasome in the interface between metabolic and inflammatory stress, involving an altered gut microbiota composition.

scholarly journals Long Noncoding RNA and mRNA Expression Profiles in the Thyroid Gland of Two Phenotypically Extreme Pig Breeds Using Ribo-Zero RNA Sequencing

Genes ◽  
2016 ◽  
Vol 7 (7) ◽  
pp. 34 ◽  
Author(s):  
Yifei Shen ◽  
Haiguang Mao ◽  
Minjie Huang ◽  
Lixing Chen ◽  
Jiucheng Chen ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Mrna Expression ◽  
Rna Sequencing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Pig Breeds
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