scholarly journals Network Analysis of the Effects of Long Non-coding RNAs in Artemisinin treatment of Atherosclerosis in APOE-/- Mice

2021 ◽  
Author(s):  
Qiao Zhao ◽  
Hongjiao Du ◽  
Xiaodong Li
Keyword(s):  
High Fat Diet ◽  
Atherosclerotic Lesion ◽  
Differentially Expressed ◽  
Future Application ◽  
Rt Pcr ◽  
Specific Amino Acid ◽  
Amino Acid Degradation ◽  
Non Coding Rnas ◽  
Medical Burden

IntroductionAtherosclerosis has become a worldwide medical burden. Our previous studies have shown that Artemisinin(ART) had the capability to reduce atherosclerosis. Emerging evidence indicates that Long non-coding RNAs(lncRNAs) are engaged in the formation of atherosclerosis. However, whether lncRNAs might participate in the mechanism through which artemisinin mitigates atherosclerosis has not been reported.Material and methodsEight-week-old apolipoprotein E deficient (APOE-/-) mice were divided into two groups, one of which was treated with Artemisinin. Red oil O staining was used to measure the sizes of Atherosclerotic lesion. We conducted deep sequencing to investigate lncRNA profiles in the aorta tissue in high-fat diet fed APOE knockdown mice with and without artemisinin treatment. CeRNA network, Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) analyses were constructed through bioinformatics analysis. RT-PCR was used to validate the differentially expressed lncRNAs.ResultsA total of 102 lncRNAs and 4,630 mRNAs were differentially expressed (p<0.05) between the Artemisinin treatment group and atherosclerosis model group. KEGG and GO analyses indicated that the categories metabolic process, specific amino acid degradation and PI3K-Akt signaling pathway are involved in the effects of artemisinin treatment in atherosclerosis(qvalue<0.05). LncRNA ENSMUST00000099676.4, ENSMUST00000143673.1, ENSMUST00000070085.5 and ENSMUST00000224554 might be engaged in treatment mechanism through which Artemisinin alleviates Atherosclerosis.ConclusionsThese findings indicated the possible mechanism and therapeutic role of lncRNAs in Artemisinin treatment of atherosclerosis and provided a theoretical basis for the future application of Artemisinin in patients with atherosclerosis.

scholarly journals Androgen Receptor-Dependent and Independent Atheroprotection by Testosterone in Male Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5428-5437 ◽  
Author(s):  
Johan Bourghardt ◽  
Anna S. K. Wilhelmson ◽  
Camilla Alexanderson ◽  
Karel De Gendt ◽  
Guido Verhoeven ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Apolipoprotein E ◽  
High Fat Diet ◽  
Atherosclerotic Lesion ◽  
Male Mice ◽  
Wild Type ◽  
High Fat ◽  
Lesion Area ◽  
Major Pathway

The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P &lt; 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P &lt; 0.001) and ARKO mice (by 24%, P &lt; 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P &lt; 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P &lt; 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.

scholarly journals Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses

2020 ◽  
Vol 11 ◽  
Author(s):  
Imran Ahmad ◽  
Araceli Valverde ◽  
Raza Ali Naqvi ◽  
Afsar R. Naqvi
Keyword(s):  
Immune Responses ◽  
Epigenetic Regulation ◽  
Innate Immune ◽  
Differentially Expressed ◽  
Immune Functions ◽  
Innate Immune Responses ◽  
Antigen Uptake ◽  
Non Coding Rnas

Macrophages (Mφ) are immune cells that exhibit remarkable functional plasticity. Identification of novel endogenous factors that can regulate plasticity and innate immune functions of Mφ will unravel new strategies to curb immune-related diseases. Long non-coding RNAs (lncRNAs) are a class of endogenous, non-protein coding, regulatory RNAs that are increasingly being associated with various cellular functions and diseases. Despite their ubiquity and abundance, lncRNA-mediated epigenetic regulation of Mφ polarization and innate immune functions is poorly studied. This study elucidates the regulatory role of lncRNAs in monocyte to Mφ differentiation, M1/M2 dichotomy and innate immune responses. Expression profiling of eighty-eight lncRNAs in monocytes and in vitro differentiated M2 Mφ identified seventeen differentially expressed lncRNAs. Based on fold-change and significance, we selected four differentially expressed lncRNAs viz., RN7SK, GAS5, IPW, and ZFAS1 to evaluate their functional impact. LncRNA knockdown was performed on day 3 M2 Mφ and the impact on polarization was assessed on day 7 by surface marker analysis. Knockdown of RN7SK and GAS5 showed downregulation of M2 surface markers (CD163, CD206, or Dectin) and concomitant increase in M1 markers (MHC II or CD23). RN7SK or GAS5 knockdown showed no significant impact on CD163, CD206, or CD23 transcripts. M1/M2 markers were not impacted by IPW or ZFAS1 knockdown. Functional regulation of antigen uptake/processing and phagocytosis, two central innate immune pathways, by candidate lncRNA was assessed in M1/M2 Mφ. Compared to scramble, enhanced antigen uptake and processing were observed in both M1/M2 Mφ transfected with siRNA targeting GAS5 and RN7SK but not IPW and ZFAS1. In addition, knockdown of RN7SK significantly augmented uptake of labelled E. coli in vitro by M1/M2 Mφ, while no significant difference was in GAS5 silencing cells. Together, our results highlight the instrumental role of lncRNA (RN7SK and GAS5)-mediated epigenetic regulation of macrophage differentiation, polarization, and innate immune functions.

scholarly journals Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

2020 ◽  
Author(s):  
Fuhui Han ◽  
Jing Li ◽  
Ranran Zhao ◽  
Lirong Liu ◽  
Lanlan Li ◽  
...  
Keyword(s):  
Target Genes ◽  
Structural Characteristics ◽  
Intramuscular Fat ◽  
Differentially Expressed ◽  
Lipid Deposition ◽  
Sequencing Data ◽  
Dual Purpose ◽  
Intramuscular Lipid ◽  
Non Coding Rnas

Abstract Background: Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and levels of IMF are affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on the lncRNAs involved in sheep IMF deposition is still in its infancy. Aohan fine-wool sheep (AFWS), one of China's most important meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of IMF deposition. We identified lncRNAs by RNA sequencing in Longissimus thoracis et lumborum (LTL) samples of sheep at two ages: 2 months (Mth-2) and 12 months (Mth-12). Results: We identified a total of 26,247 genes and 6,935 novel lncRNAs in LTL samples of sheep. Among these, 199 mRNAs and 61 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained target genes of differentially expressed lncRNAs (DELs) and performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). We found that target mRNAs were enriched in metabolic processes and developmental pathways. One pathway was significantly enriched, namely tight junction. Based on the analysis of critical target genes, we obtained seven candidate lncRNAs that potentially regulated lipid deposition and constructed a lncRNA-mRNA co-expression network that included MSTRG.4051.3-FZD4, MSTRG.16157.3-ULK1, MSTRG.21053.3-PAQR3, MSTRG.19941.2-TPI1, MSTRG.12864.1-FHL1, MSTRG.2469.2-EXOC6 and MSTRG.21381.1-NCOA1. We speculated that these candidate lncRNAs might play a role by regulating the expression of target genes. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of the sequencing data by qRT-PCR.Conclusions: Our study identified the differentially expressed mRNAs and lncRNAs during intramuscular lipid deposition in Aohan fine-wool sheep. The work may widen the knowledge about the annotation of the sheep genome and provide a working basis for investigating intramuscular fat deposition in sheep.

scholarly journals Transcriptome Analysis to Identify the Potential Role of Long non-coding RNAs in Enteric Glial Cells under Hyperglycemia

2020 ◽  
Author(s):  
Xuping Zhu ◽  
Yanyu Li ◽  
Xue Zhu ◽  
Yanmin Jiang ◽  
Xiaowei Zhu ◽  
...  
Keyword(s):  
Autonomic Neuropathy ◽  
Glial Cells ◽  
Transcriptome Analysis ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Enteric Glial Cells ◽  
Non Coding Rnas

Abstract Background Long non-coding RNAs (lncRNAs) are important mediators in the pathogenesis of diabetic gastrointestinal autonomic neuropathy, which has just been reported to have a relation to enteric glial cells (EGCs). However, the role of lncRNAs in the pathogenesis of diabetic gastrointestinal autonomic neuropathy, especially EGCs-related gastrointestinal dysfunction, has never been reported. Methods RNA sequencing technology (RNA-Seq) was used to screen the differential lncRNAs and mRNAs in EGCs under hyperglycemia (300 mmol L− 1 high glucose). Results Totally 4678 differentially expressed lncRNAs (DE lncRNAs) and 6244 differentially expressed mRNAs (DE mRNAs) were obtained. GO enrichment analysis and KEGG pathway analysis showed significant differences. 2910 and 1549 co-expressed mRNAs were respectively expressed in up-regulated and down-regulated DE lncRNA target genes. Several up- or down-regulated lncRNAs were at the key junction points of the regulatory network. Protein-protein interaction networks showed highly connected clusters were TP53, AKT1, Casp9, Casp8, Casp3, TNF, etc, which are known closely related to apoptosis. FLRT3, Fras1, and other related target genes, which revealed the potential function of lncRNAs, may be important targets for differential lncRNAs to regulate the apoptosis of glial cells induced by hyperglycemia. Conclusion In this study, the involvement of lncRNAs in EGCs under hyperglycemia was analyzed using transcriptome analysis.

scholarly journals Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

2020 ◽  
Author(s):  
Fuhui Han ◽  
Jing Li ◽  
Nan Liu ◽  
Ranran Zhao ◽  
Lirong Liu ◽  
...  
Keyword(s):  
Target Genes ◽  
Structural Characteristics ◽  
Intramuscular Fat ◽  
Differentially Expressed ◽  
Lipid Deposition ◽  
Sequencing Data ◽  
Dual Purpose ◽  
Intramuscular Lipid ◽  
Non Coding Rnas

Abstract Background: Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and levels of IMF are affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on the lncRNAs involved in sheep IMF deposition is still in its infancy. Aohan fine-wool sheep (AFWS), one of China's most important meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of IMF deposition. We identified lncRNAs by RNA sequencing in Longissimus thoracis et lumborum (LTL) samples of sheep at two ages: 2 months (Mth-2) and 12 months (Mth-12). Results: We identified a total of 26,247 genes and 6,935 novel lncRNAs in LTL samples of sheep. Among these, 199 mRNAs and 61 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained target genes of differentially expressed lncRNAs (DELs) and performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). We found that target mRNAs were enriched in metabolic processes and developmental pathways. One pathway was significantly enriched, namely tight junction. Based on the analysis of critical target genes, we obtained seven candidate lncRNAs that potentially regulated lipid deposition and constructed a lncRNA-mRNA co-expression network that included MSTRG.4051.3-FZD4, MSTRG.16157.3-ULK1, MSTRG.21053.3-PAQR3, MSTRG.19941.2-TPI1, MSTRG.12864.1-FHL1, MSTRG.2469.2-EXOC6 and MSTRG.21381.1-NCOA1. We speculated that these candidate lncRNAs might play a role by regulating the expression of target genes. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of the sequencing data by qRT-PCR.Conclusions: Our study identified the differentially expressed mRNAs and lncRNAs during intramuscular lipid deposition in Aohan fine-wool sheep. The work may widen the knowledge about the annotation of the sheep genome and provide a working basis for investigating intramuscular fat deposition in sheep.

scholarly journals Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Fuhui Han ◽  
Jing Li ◽  
Ranran Zhao ◽  
Lirong Liu ◽  
Lanlan Li ◽  
...  
Keyword(s):  
Target Genes ◽  
Structural Characteristics ◽  
Intramuscular Fat ◽  
Differentially Expressed ◽  
Lipid Deposition ◽  
Sequencing Data ◽  
Dual Purpose ◽  
Intramuscular Lipid ◽  
Non Coding Rnas

Abstract Background Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and levels of IMF are affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on the lncRNAs involved in sheep IMF deposition is still in its infancy. Aohan fine-wool sheep (AFWS), one of China’s most important meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of IMF deposition. We identified lncRNAs by RNA sequencing in Longissimus thoracis et lumborum (LTL) samples of sheep at two ages: 2 months (Mth-2) and 12 months (Mth-12). Results We identified a total of 26,247 genes and 6935 novel lncRNAs in LTL samples of sheep. Among these, 199 mRNAs and 61 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained target genes of differentially expressed lncRNAs (DELs) and performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). We found that target mRNAs were enriched in metabolic processes and developmental pathways. One pathway was significantly enriched, namely tight junction. Based on the analysis of critical target genes, we obtained seven candidate lncRNAs that potentially regulated lipid deposition and constructed a lncRNA-mRNA co-expression network that included MSTRG.4051.3-FZD4, MSTRG.16157.3-ULK1, MSTRG.21053.3-PAQR3, MSTRG.19941.2-TPI1, MSTRG.12864.1-FHL1, MSTRG.2469.2-EXOC6 and MSTRG.21381.1-NCOA1. We speculated that these candidate lncRNAs might play a role by regulating the expression of target genes. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of the sequencing data by qRT-PCR. Conclusions Our study identified the differentially expressed mRNAs and lncRNAs during intramuscular lipid deposition in Aohan fine-wool sheep. The work may widen the knowledge about the annotation of the sheep genome and provide a working basis for investigating intramuscular fat deposition in sheep.

scholarly journals Differential microRNAs expression profiles in liver from three different lifestyle modification mice models

2020 ◽  
Author(s):  
Huan Gong ◽  
Ming Zhang ◽  
Yiwen Han ◽  
Ying Zhang ◽  
Jing Pang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Target Genes ◽  
Lifestyle Modification ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Lifestyle Modifications ◽  
Enriched Categories ◽  
The Common ◽  
First Time

Abstract Background MicroRNAs play an important role in many fundamental biological and pathological processes. Defining the microRNAs profile underlying the processes by beneficial and detrimental lifestyles, including caloric restriction(CR), exercise and high-fat diet(HF), is necessary for understanding both normal physiology and the pathogenesis of metabolic disease. We used the microarray to detect microRNAs expression in livers from CR, EX and HF mice models. After predicted potential target genes of differentially expressed microRNAs with four algorithms, we applied GO and KEGG to analyze the function of predicted microRNA targets. Results We describe the overall microRNAs expression pattern, and identified 84 differentially expressed microRNAs changed by one or two or even all the three lifestyle modifications. The common and different enriched categories of gene function and main biochemical and signal transduction pathways were presented. Conclusions We provided for the first time a comprehensive and thorough comparison of microRNAs expression profiles in liver among these lifestyle modifications. With this knowledge, our findings provide us with an overall vision of microRNAs in the molecular impact of lifestyle on health as well as useful clues for future and thorough research of the role of microRNAs.

Genome-wide identification and characterization of long non-coding RNAs in Longissimus dorsi skeletal muscle of Shandong black cattle and Luxi cattle

2020 ◽  
Author(s):  
Ruili Liu ◽  
Xianxun Liu ◽  
Kun Yu ◽  
Xuejin Bai ◽  
Yajuan Dong
Keyword(s):  
Skeletal Muscle ◽  
Cell Differentiation ◽  
Muscle Cell ◽  
Muscle Development ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Longissimus Dorsi ◽  
Protein Coding ◽  
Non Coding Rnas

Abstract Background There is increasing understanding of the possible regulatory role of long non-coding RNAs (LncRNA). Studies on livestock have mainly focused on the regulation of cell differentiation, fat synthesis, and embryonic development. However, there has been little study of skeletal muscle of domestic animals and the potential role of lncRNA. Results RNA samples were collected from longissimus dorsi muscle samples of Shandong black cattle and Luxi cattle and libraries were constructed and sequenced. A total of 1415 transcripts (of which 480 were LncRNAs) were differentially expressed (P < 0.05) in the different breeds, and fourteen of these RNAs were randomly selected and validated by qPCR. We found that the most differentially expressed LncRNAs were found on chromosome 9, with 1164 within 50 kb of a protein-coding gene. In addition, Pearson's correlation coefficients of co-expression levels indicated a potential trans regulatory relationship between the differentially expressed LncRNAs and 43844 mRNAs (r > 0.9). The identified co-expressed mRNAs (MYORG, Dll1, EFNB2, SOX6, MYOCD, and MYLK3) are related to the formation of muscle structure, and enriched in muscle system process, strained muscle cell differentiation, muscle cell development, striated muscle tissue development, calcium signaling, and AMPK signaling. Additionally, we also found that some LncRNAs (LOC112444238, LOC101903367, LOC104975788, LOC112441863, LOC112449549, and LOC101907194) may interact with miRNAs related to cattle muscle growth and development. Based on this, we constructed a LncRNAs-miRNA-mRNA interaction network as the putative basis for biological regulation in cattle skeletal muscle. Interestingly, a candidate differential LncRNA (LOC104975788) and a protein-coding gene (Pax7) contain miR-133a binding sites and binding was confirmed by luciferase reporter assay. LOC104975788 may bind miR-133a competitively with Pax7, thus relieving the inhibitory effect of miR-133a on Pax7 to regulate skeletal muscle development. These results will provide the theoretical basis for further study of LncRNA regulation and activity in different cattle breeds. Conclusions The data obtained in this study were used to predict muscle-related LncRNAs-miRNA-mRNA interaction networks, which can help elucidate the molecular mechanism of cattle muscle development. These results can be used to facilitate livestock breeding and improve livestock production.

scholarly journals Proteomics Analysis of Testis of Rats Fed a High-Fat Diet

2018 ◽  
Vol 47 (1) ◽  
pp. 378-389 ◽  
Author(s):  
Xiu-Yan Yang ◽  
Yu-jie Gu ◽  
Tian An ◽  
Jia-Xian Liu ◽  
Yan-Yun Pan ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Metabolic Pathways ◽  
High Fat Diet ◽  
Male Fertility ◽  
Enrichment Analysis ◽  
Normal Diet ◽  
Differentially Expressed ◽  
High Fat ◽  
Non Coding Rnas ◽  
Reproductive Processes

Background/Aims: The adverse effects of obesity on male fertility have been widely reported. In recent years, the relationship between the differential expression of proteins and long non-coding RNAs with male reproductive disease has been reported. However, the exact mechanism in underlying obesity-induced decreased male fertility remains unclear. Methods: We used isobaric tags for relative and absolute quantification to identify differential protein expression patterns in the testis of rats fed a high-fat diet and normal diet. A microarray-based gene expression analysis protocol was used to compare the differences in long non-coding RNAs in high-fat diet-fed and normal diet-fed rats. Five obviously upregulated or downregulated proteins were examined using western blot to verify the accuracy of their expression. Then, we carried out functional enrichment analysis of the differentially expressed proteins using gene ontology and pathway analysis. Finally, the metabolic Gene Ontology terms and pathways involved in the differential metabolites were analyzed using the MetaboAnalyst 2.0 software to explore the co-expression relationship between long non-coding RNAs and proteins. Results: We found 107 proteins and 263 long non-coding RNAs differentially expressed between rats fed a high-fat diet and normal diet. The Gene Ontology term enrichment analysis showed that the protein function most highly enriched was related to negative regulation of reproductive processes. We also found five Gene Ontology terms and two metabolic pathways upregulated or downregulated for both proteins and long non-coding RNAs. Conclusion: The study revealed different expression levels for both proteins and long non-coding RNAs and showed that the function and metabolic pathways of differently expressed proteins were related to reproductive processes. The Gene Ontology terms and metabolic pathways upregulated or downregulated in both proteins and long non-coding RNAs may provide new candidates to explore the mechanisms of obesity-induced male infertility for both protein and epigenetic pathways.

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