scholarly journals Exploring Differential Transcriptome between Jejunal and Cecal Tissue of Broiler Chickens

Animals ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 221 ◽  
Author(s):  
Micol Bertocchi ◽  
Federico Sirri ◽  
Orazio Palumbo ◽  
Diana Luise ◽  
Giuseppe Maiorano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Rna Extraction ◽  
Gene Clusters ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Peroxisome Proliferator ◽  
Related Gene ◽  
Peroxisome Proliferator Activated Receptor ◽  
Gene Sets

The study proposed an exploratory functional analysis on differential gene expression of the jejunum and of cecum in chickens. For this study, 150 Ross 308 male chickens were randomly allotted in six pens (25 birds/pen) and fed the same commercial diet. From 19 birds of 42 days of age, jejunum and cecum mucosae were collected for RNA extraction for transcriptome microarray analysis. Differentially expressed genes (DEGs) submitted to DAVID (Database for Annotation, Visualization, and Integrated Discovery) and Gene Set Enrichment Analysis (GSEA) software evidenced enriched gene clusters for biological functions differentiated in the tissues. DAVID analysis in the jejunum showed enriched annotations for cell membrane integral components, PPAR (peroxisome proliferator-activated receptor) signaling pathway, and peroxisome and lipid metabolism, and showed DEGs for gluconeogenesis, not previously reported in chicken jejunum. The cecum showed enriched annotations for disulfide bond category, cysteine and methionine metabolism, glycoprotein category, cell cycle, and extracellular matrix (ECM). GSEA analysis in the jejunum showed peroxisome and PPAR signaling pathway-related gene sets, as found with DAVID, and gene sets for immune regulation, tryptophan and histidine metabolism, and renin–angiotensin system, like in mammals. The cecum showed cell cycle and regulation processes, as well as ECM receptor interaction and focal adhesion-related gene sets. Typical intestinal functions specific for the gut site and interesting functional genes groups emerged, revealing tissue-related key aspects which future studies might take advantage of.

scholarly journals Assessment of the Mode of Action Underlying the Effects of GenX in Mouse Liver and Implications for Assessing Human Health Risks

2020 ◽  
Vol 48 (3) ◽  
pp. 494-508 ◽  
Author(s):  
Grace A. Chappell ◽  
Chad M. Thompson ◽  
Jeffrey C. Wolf ◽  
John M. Cullen ◽  
James E. Klaunig ◽  
...  
Keyword(s):  
Human Health ◽  
Mode Of Action ◽  
Human Health Risk ◽  
Gene Set Enrichment Analysis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peroxisomal Enzyme ◽  
Gene Sets ◽  
Liver Changes

GenX is an alternative to environmentally persistent long-chain perfluoroalkyl and polyfluoroalkyl substances. Mice exposed to GenX exhibit liver hypertrophy, elevated peroxisomal enzyme activity, and other apical endpoints consistent with peroxisome proliferators. To investigate the potential role of peroxisome proliferator-activated receptor alpha (PPARα) activation in mice, and other molecular signals potentially related to observed liver changes, RNA sequencing was conducted on paraffin-embedded liver sections from a 90-day subchronic toxicity study of GenX conducted in mice. Differentially expressed genes were identified for each treatment group, and gene set enrichment analysis was conducted using gene sets that represent biological processes and known canonical pathways. Peroxisome signaling and fatty acid metabolism were among the most significantly enriched gene sets in both sexes at 0.5 and 5 mg/kg GenX; no pathways were enriched at 0.1 mg/kg. Gene sets specific to the PPARα subtype were significantly enriched. These findings were phenotypically anchored to histopathological changes in the same tissue blocks: hypertrophy, mitoses, and apoptosis. In vitro PPARα transactivation assays indicated that GenX activates mouse PPARα. These results indicate that the liver changes observed in GenX-treated mice occur via a mode of action (MOA) involving PPARα, an important finding for human health risk assessment as this MOA has limited relevance to humans.

scholarly journals Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Leng ◽  
Dan Fan ◽  
Zhong Ren ◽  
Qiaoying Li
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysm ◽  
Signaling Pathway ◽  
Aneurysm Rupture ◽  
Cytokine Receptor ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Regulatory Pathways ◽  
Ruptured Intracranial Aneurysm ◽  
Neurotrophin Signaling

Abstract Background This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA). Methods Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337. Results Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337. Conclusion LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.

scholarly journals PPARγ Activation Inhibits Growth and Survival of Human Endometriotic Cells by Suppressing Estrogen Biosynthesis and PGE2 Signaling.

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4803-4813 ◽  
Author(s):  
Dan I. Lebovic ◽  
Shahryar K. Kavoussi ◽  
JeHoon Lee ◽  
Sakhila K. Banu ◽  
Joe A. Arosh
Keyword(s):  
Cell Cycle ◽  
Stromal Cells ◽  
Cell Cycle Regulation ◽  
Chronic Inflammatory Disease ◽  
Reproductive Age ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Growth And Survival ◽  
Cycle Regulation ◽  
Estrogen Biosynthesis

Endometriosis is a chronic inflammatory disease of reproductive age women leading to chronic pelvic pain and infertility. Current antiestrogen therapies are temporizing measures, and endometriosis often recurs. Potential nonestrogenic or nonsteroidal targets are needed for treating endometriosis. Peroxisome proliferator-activated receptor (PPAR)γ, a nuclear receptor, is activated by thiazolidinediones (TZDs). In experimental endometriosis, TZDs inhibit growth of endometriosis. Clinical data suggest potential use of TZDs for treating pain and fertility concurrently in endometriosis patients. Study objectives were to 1) determine the effects of PPARγ action on growth and survival of human endometriotic epithelial and stromal cells and 2) identify the underlying molecular links between PPARγ activation and cell cycle regulation, apoptosis, estrogen biosynthesis, and prostaglandin E2 biosynthesis and signaling in human endometriotic epithelial and stromal cells. Results indicate that activation of PPARγ by TZD ciglitazone 1) inhibits growth of endometriotic epithelial cells 12Z up to 35% and growth of endometriotic stromal cells 22B up to 70% through altered cell cycle regulation and intrinsic apoptosis, 2) decreases expression of PGE2 receptors (EP)2 and EP4 mRNAs in 12Z and 22B cells, and 3) inhibits expression and function of P450 aromatase mRNA and protein and estrone production in 12Z and 22B cells through EP2 and EP4 in a stromal-epithelial cell-specific manner. Collectively, these results indicate that PGE2 receptors EP2 and EP4 mediate actions of PPARγ by incorporating multiple cell signaling pathways. Activation of PPARγ combined with inhibition of EP2 and EP4 may emerge as novel nonsteroidal therapeutic targets for endometriosis-associated pain and infertility, if clinically proven safe and efficacious.

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ

2021 ◽  
Author(s):  
Jing Li ◽  
Kewei Xu ◽  
Hao Ding ◽  
Qiaozhen Xi
Keyword(s):  
Locomotor Activity ◽  
Signaling Pathway ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Ethanol Consumption ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Tnf Α

Abstract Aims Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. Methods The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. Results GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Conclusions Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

CENPF/CDK1 Signaling Pathway Enhances the Progression of Adrenocortical Carcinoma by Regulating the G2/M-phase Cell Cycle

2021 ◽  
Author(s):  
Yugang Huang ◽  
Dan Li ◽  
Li Wang ◽  
Xiaomin Su ◽  
Xian-bin Tang
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Adrenocortical Carcinoma ◽  
Immune Cell ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Phase Cell ◽  
Aberrant Expression ◽  
M Phase

Abstract Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor and prone to local invasion and metastasis. While, overexpressed Centromere Protein F (CENPF) is closely related to oncogenesis of various neoplasms, including ACC. However, the prognosis and exact biological function of CENPF in ACC remains largely unclear. In present essay, the expression of CENPF in human ACC samples, GEO and TCGA databases depicted that CENPF were overtly hyper-expressed in ACC patients and positively correlated with tumor stage. The aberrant expression of CENPF was significantly correlated with unfavorable overall survival (OS) in ACC patients. Then, the application of gene-set enrichment analysis (GSEA) declared that CENPF was mainly involved in the G2/M-phase mediated cell cycle and p53 signaling pathway. Further, a small RNA interference experiment was conducted to demonstrate that the interaction between CENPF and CDK1 enhanced the G2/M-phase transition of mitosis, cell proliferation and might induce p53 mediated anti-tumor effect in human ACC cell line, SW13 cells. Lastly, two available therapeutic strategies, including immunotherapy and chemotherapy, have been further probed. Immune infiltration analysis highlighted that ACC patients with high CENPF expression harbored significantly different immune cell populations, and high TMB/MSI score. Then, the gene-drug interaction network stated that CENPF inhibitors, such as Cisplatin, Sunitinib, and Etoposide, might serve as potential drugs for the therapy of ACC. Briefly, CENPF and related genes might be served as a novel prognostic biomarker or latent therapeutic target for ACC patients.

scholarly journals Anxa2 gene silencing attenuates obesity-induced insulin resistance by suppressing the NF-κB signaling pathway

2019 ◽  
Vol 316 (2) ◽  
pp. C223-C234 ◽  
Author(s):  
Yong Wang ◽  
Yun-Sheng Cheng ◽  
Xiao-Qiang Yin ◽  
Gang Yu ◽  
Ben-Li Jia
Keyword(s):  
Insulin Resistance ◽  
Gene Silencing ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Cell Model ◽  
Global Scale ◽  
Differentially Expressed ◽  
Cytokine Signaling ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Insulin resistance (IR) continues to pose a major threat to public health due to its role in the pathogenesis of metabolic syndrome and its ever-increasing prevalence on a global scale. The aim of the current study was to investigate the efficacy of Anxa2 in obesity-induced IR through the mediation of the NF-κB signaling pathway. Microarray analysis was performed to screen differentially expressed genes associated with obesity. To verify whether Anxa2 was differentially expressed in IR triggered by obesity, IR mouse models were established in connection with a high-fat diet (HFD). In the mouse IR model, the role of differentially expressed Anxa2 in glycometabolism and IR was subsequently detected. To investigate the effect of Anxa2 on IR and its correlation with inflammation, a palmitic acid (PA)-induced IR cell model was established, with the relationship between Anxa2 and the NF-κB signaling pathway investigated accordingly. Anxa2 was determined to be highly expressed in IR. Silencing Anxa2 was shown to inhibit IR triggered by obesity. When Anxa2 was knocked down, elevated expression of phosphorylated insulin receptor substrate 1 (IRS1), IRS1 and peroxisome proliferator-activated receptor coactivator-1a, and glucose tolerance and insulin sensitivity along with 2-deoxy-d-glucose uptake was detected, whereas decreased expression of suppressor of cytokine signaling 3, IL-6, IL-1β, TNF-α, and p50 was observed. Taken together, the current study ultimately demonstrated that Anxa2 may be a novel drug strategy for IR disruption, indicating that Anxa2 gene silencing is capable of alleviating PA or HFD-induced IR and inflammation through its negative regulatory role in the process of p50 nuclear translocation of the NF-κB signaling pathway.

Regulator 1-Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Signaling Pathway in Investigating the Pathological Characteristics and Molecular Mechanism of Liver Cirrhosis Complicated by Acute Kidney Injury

2022 ◽  
Vol 12 (1) ◽  
pp. 112-120
Author(s):  
Jieqi Gong ◽  
Huanhua Lu
Keyword(s):  
Acute Kidney Injury ◽  
Liver Cirrhosis ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Kidney Injury ◽  
Male Rats ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Duct Ligation

The objective of this study was to investigate the molecular mechanism of the histopathological characteristics of liver cirrhosis (LC) complicated with acute kidney injury (AKI) and the signaling pathway of silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) during the pathogenesis of LC. 20 healthy male rats with AKI complicated by laparoscopic cholecystectomy were selected and divided randomly into control group (C group), lipopolysaccharide (LPS) group, bile duct ligation (BDL) group, and model group (lipopolysaccharide+BDL) (D group). The indexes of all the rats were determined, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), sarcoplasmic enzyme (Scr), and blood urea nitrogen (BUN); the SIRT1 and PGC-1α expressions in renal tissues of rats from each group was detected. Results showed that the AST and ALT levels in BDL group and D group were higher markedly than those before surgery (P < 0.05). The serum levels of Scr and BUN in D group 4 hours after LPS injection increased hugely compared with before injection (P < 0.05). Compared with BDL group, the protein levels of SIRT1 and PGC-1α in renal tissue of group D were decreased sharply (P < 0.05), and the SIRT1 protein expression was positively correlated with PGC-1α (r = 0.836 and P < 0.01). When LC were complicated with AKI, SIRT1 activity was reduced and PGC-1α expression was inhibited. Moreover, SIRT1-PGC-1α signaling pathway played a protective role in pathogenesis of LC complicated with AKI.

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