P476SREBF1, SREBF2 and their target genes expression is different in wistar and SHR rats under high cholesterol treatment conditions

Previous research has revealed that miR-215 might be an important miRNA regulating weaned piglets’ resistance to Escherichia coli (E. coli) F18. In this study, target genes of miR-215 were identified by RNA-seq, bioinformatics analysis and dual luciferase detection. The relationship between target genes and E. coli infection was explored by RNAi technology, combined with E. coli stimulation and enzyme linked immunosorbent assay (ELISA) detection. Molecular regulating mechanisms of target genes expression were analyzed by methylation detection of promoter regions and dual luciferase activity assay of single nucleotide polymorphisms (SNPs) in core promoter regions. The results showed that miR-215 could target EREG, NIPAL1 and PTPRU genes. Expression levels of three genes in porcine intestinal epithelial cells (IPEC-J2) in the RNAi group were significantly lower than those in the negative control pGMLV vector (pGMLV-NC) group after E. coli F18 stimulation, while cytokines levels of TNF-α and IL-1β in the RNAi group were significantly higher than in the pGMLV-NC group. Variant sites in the promoter region of three genes could affect their promoter activities. These results suggested that miR-215 could regulate weaned piglets’ resistance to E. coli F18 by targeting EREG, NIPAL1 and PTPRU genes. This study is the first to annotate new biological functions of EREG, NIPAL1 and PTPRU genes in pigs, and provides a new experimental basis and reference for the research of piglets disease-resistance breeding.

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Identifying stress responsive genes using overlapping communities in co-expression networks

BMC Bioinformatics ◽

10.1186/s12859-021-04462-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Camila Riccio-Rengifo ◽

Jorge Finke ◽

Camilo Rocha

Keyword(s):

Salt Stress ◽

Target Genes ◽

Specific Treatment ◽

Search Space ◽

Shoot Biomass ◽

Lasso Regression ◽

Overlapping Communities ◽

Regulatory Domains ◽

Treatment Conditions ◽

Highly Sensitive

Abstract Background This paper proposes a workflow to identify genes that respond to specific treatments in plants. The workflow takes as input the RNA sequencing read counts and phenotypical data of different genotypes, measured under control and treatment conditions. It outputs a reduced group of genes marked as relevant for treatment response. Technically, the proposed approach is both a generalization and an extension of WGCNA. It aims to identify specific modules of overlapping communities underlying the co-expression network of genes. Module detection is achieved by using Hierarchical Link Clustering. The overlapping nature of the systems’ regulatory domains that generate co-expression can be identified by such modules. LASSO regression is employed to analyze phenotypic responses of modules to treatment. Results The workflow is applied to rice (Oryza sativa), a major food source known to be highly sensitive to salt stress. The workflow identifies 19 rice genes that seem relevant in the response to salt stress. They are distributed across 6 modules: 3 modules, each grouping together 3 genes, are associated to shoot K content; 2 modules of 3 genes are associated to shoot biomass; and 1 module of 4 genes is associated to root biomass. These genes represent target genes for the improvement of salinity tolerance in rice. Conclusions A more effective framework to reduce the search-space for target genes that respond to a specific treatment is introduced. It facilitates experimental validation by restraining efforts to a smaller subset of genes of high potential relevance.

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Impact of SCP-2/SCP-x gene ablation and dietary cholesterol on hepatic lipid accumulation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00460.2014 ◽

2015 ◽

Vol 309 (5) ◽

pp. G387-G399 ◽

Cited By ~ 22

Author(s):

Devon Klipsic ◽

Danilo Landrock ◽

Gregory G. Martin ◽

Avery L. McIntosh ◽

Kerstin K. Landrock ◽

...

Keyword(s):

Fatty Acid ◽

Cholesteryl Ester ◽

Hepatic Steatosis ◽

Target Genes ◽

High Cholesterol Diet ◽

Carrier Protein ◽

Sterol Carrier Protein ◽

Cholesterol Diet ◽

High Cholesterol ◽

Fatty Acid Binding

While a high-cholesterol diet induces hepatic steatosis, the role of intracellular sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) proteins is unknown. We hypothesized that ablating SCP-2/SCP-x [double knockout (DKO)] would impact hepatic lipids (cholesterol and cholesteryl ester), especially in high-cholesterol-fed mice. DKO did not alter food consumption, and body weight (BW) gain decreased especially in females, concomitant with hepatic steatosis in females and less so in males. DKO-induced steatosis in control-fed wild-type (WT) mice was associated with 1) loss of SCP-2; 2) upregulation of liver fatty acid binding protein (L-FABP); 3) increased mRNA and/or protein levels of sterol regulatory element binding proteins (SREBP1 and SREBP2) as well as increased expression of target genes of cholesterol synthesis ( Hmgcs1 and Hmgcr) and fatty acid synthesis ( Acc1 and Fas); and 4) cholesteryl ester accumulation was also associated with increased acyl-CoA cholesterol acyltransferase-2 (ACAT2) in males. DKO exacerbated the high-cholesterol diet-induced hepatic cholesterol and glyceride accumulation, without further increasing SREBP1, SREBP2, or target genes. This exacerbation was associated both with loss of SCP-2 and concomitant downregulation of Ceh/Hsl, apolipoprotein B (ApoB), MTP, and/or L-FABP protein expression. DKO diminished the ability to secrete excess cholesterol into bile and oxidize cholesterol to bile acid for biliary excretion, especially in females. This suggested that SCP-2/SCP-x affects cholesterol transport to particular intracellular compartments, with ablation resulting in less to the endoplasmic reticulum for SREBP regulation, making more available for cholesteryl ester synthesis, for cholesteryl-ester storage in lipid droplets, and for bile salt synthesis and/or secretion. These alterations are significant findings, since they affect key processes in regulation of sterol metabolism.

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Role of the Nrf2-ARE Pathway in Liver Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/763257 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 83

Author(s):

Sang Mi Shin ◽

Ji Hye Yang ◽

Sung Hwan Ki

Keyword(s):

Liver Diseases ◽

Target Genes ◽

Antioxidant Response ◽

Related Factor ◽

Genes Expression ◽

Wide Range ◽

Range Of Functions ◽

Central Organ ◽

Essential Transcription Factor

The liver is a central organ that performs a wide range of functions such as detoxification and metabolic homeostasis. Since it is a metabolically active organ, liver is particularly susceptible to oxidative stress. It is well documented that liver diseases including hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are highly associated with antioxidant capacity. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. It is activated in response to electrophiles and induces its target genes by binding to the antioxidant response element (ARE). Therefore, the roles of the Nrf2-ARE pathway in liver diseases have been extensively investigated. Studies from several animal models suggest that the Nrf2-ARE pathway collectively exhibits diverse biological functions against viral hepatitis, alcoholic and nonalcoholic liver disease, fibrosis, and cancer via target gene expression. In this review, we will discuss the role of the Nrf2-ARE pathway in liver pathophysiology and the potential application of Nrf2 as a therapeutic target to prevent and treat liver diseases.

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Feeding of Enterococcus faecium NCIMB 10415 Leads to Intestinal miRNA-423-5p-Induced Regulation of Immune-Relevant Genes

Applied and Environmental Microbiology ◽

10.1128/aem.04044-15 ◽

2016 ◽

Vol 82 (8) ◽

pp. 2263-2269 ◽

Cited By ~ 12

Author(s):

Susanne Kreuzer-Redmer ◽

Jennifer C. Bekurtz ◽

Danny Arends ◽

Ralf Bortfeldt ◽

Barbara Kutz-Lohroff ◽

...

Keyword(s):

Mode Of Action ◽

Enterococcus Faecium ◽

Target Genes ◽

Immune Cell ◽

Animal Health ◽

Luciferase Reporter ◽

Content Type ◽

Immunoglobulin Kappa ◽

Genes Expression ◽

Reporter Assays

ABSTRACTProbiotics are widely used in human and animal health, but little is known about the mode of action of probiotics. One possible mechanism at the molecular level could be an influence on microRNAs (miRNAs) and the related immune-relevant target genes. Here, we analyzed differential expression of miRNA and potential target genes of ileal and jejunal lymphatic tissues fromEnterococcus faeciumNCIMB 10415-fed piglets versus untreated controls by using next-generation sequencing. We identified miR-423-5p as being greatly affected by the treatment group (2.32-fold;P= 0.014). Validation by reverse transcription-quantitative PCR (RT-qPCR) confirmed a significant upregulation of miR-423-5p (2.11-fold;P= 0.03) and, additionally, downregulation of the important immune-relevant immunoglobulin lambda light C region (IGLC) (0.61-fold;P= 0.03) and immunoglobulin kappa constant (IGKC) (0.69-fold;P= 0.04) target genes. Expression analysis of miR-423-5p and IGLC at different age points shows a clear anticorrelated relationship. Luciferase reporter assays with a HeLa cell line verified IGLC as a target of miR-423-5p. The results provided evidence for an effect of feeding ofE. faeciumon the expression of miR-423-5p and on the regulation of the IGLC gene through miR-423-5p. This might be a possible mode of action ofE. faeciumon immune cell regulation in the small intestine.

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Cryptotanshinone Reverses Cisplatin Resistance of Human Lung Carcinoma A549 Cells through Down-Regulating Nrf2 Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000430398 ◽

2015 ◽

Vol 37 (2) ◽

pp. 816-824 ◽

Cited By ~ 27

Author(s):

Chen Xia ◽

Xupeng Bai ◽

Xiangyu Hou ◽

Xiaoli Gou ◽

Yongtao Wang ◽

...

Keyword(s):

Target Genes ◽

Salvia Miltiorrhiza ◽

A549 Cells ◽

Nrf2 Pathway ◽

Expression Levels ◽

Endogenous Expression ◽

Sulforhodamine B ◽

Genes Expression ◽

Human Lung Carcinoma ◽

Nrf2 Expression

Background/Aims: To explore whether Nrf2 was associated with drug-resistance in cisplatin resistant A549 (A549/DDP) cells, and if cryptotanshinone (CTS), one of the bioactive compounds isolated from the roots of Salvia miltiorrhiza Bunge (Danshen), could enhance the sensitivity in A549/DDP cells towards cisplatin. Methods: A549 and A549/DDP cells were subjected to various treatments, and then Sulforhodamine B (SRB) assay, flow cytometry analysis and western immunoblotting analysis were applied to determine IC50, apoptotic status and expressions of Nrf2 and its downstream genes. Results: The endogenous expression levels of Nrf2 as well as its target genes including GCLC, GCLM, HO-1, NQO1 and MRP1 were much higher in A549/DDP cells than those of A549 cells and the susceptibility of A549/DDP cells to cisplatin was partially restored by silencing Nrf2. The combination of CTS and cisplatin led to cell death and apoptosis through sensitizing A549/DDP cells towards cisplatin compared with cisplatin mono-treatment, however, this reversal role could be abolished by Nrf2 knockdown. Specifically, CTS obviously diminished Nrf2 expression, thus contributing to the decrease of Nrf2-target genes expression levels. Meanwhile, we also discovered that CTS triggered several other signals involving in chemoresistance such as MAPKs, Akt and STAT3 pathway. Conclusion: Our data indicated CTS may be developed as a potential sensitizer cooperating with anticancer drugs to combat chemoresistant carcinoma through the inhibition of the Nrf2 pathway.

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Association between plasma selenium level and NRF2 target genes expression in humans

Journal of Trace Elements in Medicine and Biology ◽

10.1016/j.jtemb.2014.11.008 ◽

2015 ◽

Vol 30 ◽

pp. 102-106 ◽

Cited By ~ 19

Author(s):

Edyta Reszka ◽

Edyta Wieczorek ◽

Ewa Jablonska ◽

Beata Janasik ◽

Wojciech Fendler ◽

...

Keyword(s):

Target Genes ◽

Selenium Level ◽

Plasma Selenium ◽

Genes Expression

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The effect of treatment conditions on color characteristics and measure of cholesterol removal from milk by beta-cyclodextrin application

Potravinarstvo Slovak Journal of Food Sciences ◽

10.5219/1557 ◽

2021 ◽

Vol 15 ◽

pp. 192-198

Author(s):

Lukáš Kolarič ◽

Peter Šimko

Keyword(s):

Large Scale ◽

Mixing Time ◽

Cholesterol Content ◽

High Cholesterol ◽

Cholesterol Removal ◽

Mixing Speed ◽

Treatment Conditions ◽

Cholesterol Intake ◽

Effect Of Treatment

Long-term high cholesterol intake is one of the most critical risk factors of cardiovascular diseases (CVD). As milk and dairy products are rich in cholesterol and are consumed on a large scale, the production of low-cholesterol content products could decrease effectively high cholesterol intake what would be one of the crucial steps in CVD prevention. Thus, this study is aimed at optimization of treatment conditions (mixing speed, time, and temperature) and β-cyclodextrin addition affecting the measure of cholesterol removal in milk. As found, the optimal conditions were identified such as mixing speed 840 rpm, mixing time 10 min, and the temperature of mixing 25 °C while the most effectivity in cholesterol decrease content (98.1%) was observed after 2.0% β-cyclodextrin addition. The cholesterol removal process did not affect considerably the lightness values L* of treated milk, slight differences were noticed in terms of a* and b* color values but ΔE values were statistically insignificant, i.e., the process of cholesterol removal did not affect visual characteristics of treated milk. So, these conditions can be applied for the production of milk base functional foods with the decreased cholesterol content.

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HspB1 Overexpression Improves Lifespan and Stress Resistance in an Invertebrate Model

The Journals of Gerontology Series A ◽

10.1093/gerona/glab296 ◽

2021 ◽

Author(s):

Courtney Carroll Alexander ◽

Erin Munkáscy ◽

Haven Tillmon ◽

Tamara Fraker ◽

Jessica Scheirer ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Stress Resistance ◽

Target Genes ◽

Small Heat Shock Protein ◽

Life Extension ◽

Mole Rat ◽

Genes Expression ◽

Heat Response ◽

High Level

Abstract To explore the role of the small heat shock protein beta 1 (HspB1, also known as Hsp25 in rodents and Hsp27 in humans) in longevity, we created a Caenorhabiditis elegans model with a high level of ubiquitous expression of the naked mole-rat HspB1 protein. The worms showed increased lifespan under multiple conditions and also increased resistance to heat stress. RNAi experiments suggest that HspB1-induced life extension is dependent on the transcription factors skn-1 (Nrf2) and hsf-1 (Hsf1). RNAseq from HspB1 worms showed an enrichment in several skn-1 target genes, including collagen proteins and lysosomal genes. Expression of HspB1 also improved functional outcomes regulated by SKN-1, specifically oxidative stress resistance and pharyngeal integrity. This work is the first to link a small heat shock protein with collagen function, suggesting a novel role for HspB1 as a hub between canonical heat response signaling and SKN-1 transcription.

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Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer

10.1101/388264 ◽

2018 ◽

Author(s):

Charles C. Guo ◽

Tadeusz Majewski ◽

Li Zhang ◽

Hui Yao ◽

Jolanta Bondaruk ◽

...

Keyword(s):

Bladder Cancer ◽

Target Genes ◽

Molecular Subtype ◽

Genomic Analysis ◽

Urothelial Bladder Cancer ◽

Urothelial Carcinomas ◽

High Propensity ◽

Genes Expression ◽

Urothelial Bladder ◽

Muscle Invasive

SUMMARYThe sarcomatoid variant of urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report a comprehensive genomic analysis of 28 cases of SARCs and 84 cases of conventional urothelial carcinomas (UCs), with the TCGA cohort of 408 muscle-invasive bladder cancers serving as the reference. SARCs showed a distinct mutational landscape with enrichment ofTP53, RB1, and PIK3CAmutations. They were related to the basal molecular subtype of conventional UCs and could be divided into epithelial/basal and more clinically aggressive mesenchymal subsets based on TP63 and its target genes expression levels. Other analyses revealed that SARCs are driven by downregulation of homotypic adherence genes and dysregulation of cell cycle and EMT networks, and nearly half exhibited a heavily infiltrated immune phenotype. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer.

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