scholarly journals N6-Methyladenosine Methylation Analysis of Long Noncoding RNAs and mRNAs in IPEC-J2 Cells Treated With Clostridium perfringens beta2 Toxin

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaojiao Yang ◽  
Qiaoli Yang ◽  
Juanli Zhang ◽  
Xiaoli Gao ◽  
Ruirui Luo ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Clostridium Perfringens ◽  
Defense Response ◽  
Target Genes ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Infectious Diarrhea ◽  
Type C

BackgroundThe n6-methyladenosine (m6A) modification is present widely in mRNAs and long non-coding RNAs (lncRNAs), and is related to the occurrence and development of certain diseases. However, the role of m6A methylation in Clostridium perfringens type C infectious diarrhea remains unclear.MethodsHere, we treated intestinal porcine jejunum epithelial cells (IPEC-J2 cells) with Clostridium perfringens beta2 (CPB2) toxin to construct an in vitro model of Clostridium perfringens type C (C. perfringens type C) infectious diarrhea, and then used methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to identify the methylation profiles of mRNAs and lncRNAs in IPEC-J2 cells.ResultsWe identified 6,413 peaks, representing 5,825 m6A-modified mRNAs and 433 modified lncRNAs, of which 4,356 m6A modified mRNAs and 221 m6A modified lncRNAs were significantly differential expressed between the control group and CPB2 group. The motif GGACU was enriched significantly in both the control group and the CPB2 group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis showed that the differentially methylated modified mRNAs were mainly enriched in Hippo signaling pathway and Wnt signaling pathway. In addition, the target genes of the differentially m6A modified lncRNAs were related to defense response to virus and immune response. For example, ENSSSCG00000042575, ENSSSCG00000048701 and ENSSSCG00000048785 might regulate the defense response to virus, immune and inflammatory response to resist the harmful effects of viruses on cells.ConclusionIn summary, this study established the m6A transcription profile of mRNAs and lncRNAs in IPEC-J2 cells treated by CPB2 toxin. Further analysis showed that m6A-modified RNAs were related to defense against viruses and immune response after CPB2 toxin treatment of the cells. Threem6A-modified lncRNAs, ENSSSCG00000042575, ENSSSCG00000048785 and ENSSSCG00000048701, were most likely to play a key role in CPB2 toxin-treated IPEC-J2 cells. The results provide a theoretical basis for further research on the role of m6A modification in piglet diarrhea.

scholarly journals Aberrant Expressional Profiling of Known MicroRNAs in the Liver of Silver Carp (Hypophthalmichthys molitrix) Following Microcystin-LR Exposure Based on samllRNA Sequencing

Toxins ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 41 ◽  
Author(s):  
Yiyi Feng ◽  
Xi Chen ◽  
Junguo Ma ◽  
Bangjun Zhang ◽  
Xiaoyu Li
Keyword(s):  
Signaling Pathway ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Liver Toxicity ◽  
Silver Carp ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Control Group ◽  
Hypophthalmichthys Molitrix ◽  
Multiple Organs

Microcystin-LR (MC-LR) poses a serious threat to human health due to its hepatotoxicity. However, the specific molecular mechanism of miRNAs in MC-LR-induced liver injury has not been determined. The aim of the present study was to determine whether miRNAs are regulated in MC-LR-induced liver toxicity by using high-throughput sequencing. Our research demonstrated that 53 miRNAs and 319 miRNAs were significantly changed after 24 h of treatment with MC-LR (50 and 200 μg/kg, respectively) compared with the control group. GO enrichment analysis revealed that these target genes were related to cellular, metabolic, and single-organism processes. Furthermore, KEGG pathway analysis demonstrated that the target genes of differentially expressed miRNAs in fish liver were primarily involved in the insulin signaling pathway, PPAR signaling pathway, Wnt signaling pathway, and transcriptional misregulation in cancer. Moreover, we hypothesized that 4 miRNAs (miR-16, miR-181a-3p, miR-451, and miR-223) might also participate in MC-LR-induced toxicity in multiple organs of the fish and play regulatory roles according to the qPCR analysis results. Taken together, our results may help to elucidate the biological function of miRNAs in MC-LR-induced toxicity.

scholarly journals Evaluation of the Effect of Probiotic Administration on Gene Expression in Goat Blood

2017 ◽  
Vol 7 (1) ◽  
pp. 88 ◽  
Author(s):  
Kingsley Ekwemalor ◽  
Emmanuel Asiamah ◽  
Bertha Osei ◽  
Hamid Ismail ◽  
Mulumebet Worku
Keyword(s):  
Immune Response ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Adaptive Immune Response ◽  
Control Group ◽  
Sterile Water ◽  
Adaptive Immune ◽  
Expression Of Genes ◽  
Probiotic Treatment

The objective of this study was to assess the molecular impact of probiotic administration on genes involved in homeostasis and immunity in goat blood. Following initial screening for infection, one-week post weaning, female SpanishXBoer goats were drenched daily with the recommended doses of FASTtrak microbial pack (Conklin Company Inc., Shakopee, MN) in 10 mL sterile water over an 8-week period. The control group were given sterile water. Blood samples were collected weekly. Total RNA was isolated from blood collected at the beginning of the study (week 0) and at the end of the study (week 8) using Tri-reagent and then reverse-transcribed to cDNA using the Ambion-Retroscript kit. Quantification of genes was performed in the CFX96TM Biorad Real-Time PCR detection system with the addition of the dye SYBR green. The cow Wingless (Wnt) signaling pathway, Human Innate & Adaptive Immune Responses and the Cow Inflammatory Cytokine & Receptors RT² Profiler™ PCR Arrays (QIAGEN, Valencia, CA) were used to profile the expression of 84 genes involved in each pathway. Probiotic treatment had no effect on body weight, body condition, fecal egg count and RNA concentration (p>0.05). Packed cell volume and FAMACHA scores were significantly improved by probiotic administration. Results from RT-PCR showed increased expression of genes in innate and adaptive immune response, cytokine and Wnt pathways in response to probiotics. Probiotics induced the expression of 32 genes involved in innate and adaptive immune response inflammatory cytokines, and 48 genes involved in the Wnt signaling pathway. This study provides evidence for a systematic effect of oral probiotic administration on expression of genes involved in immunity and homeostasis in goat blood.

scholarly journals MicroRNA Dysregulation in the Hippocampus of Rats with Noise-Induced Hearing Loss

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Seungmin Ha ◽  
Kyung Woon Kim ◽  
So Min Lee ◽  
Chang Ho Lee ◽  
So Young Kim
Keyword(s):  
Hearing Loss ◽  
Signaling Pathway ◽  
Target Genes ◽  
Noise Exposure ◽  
Wnt Signaling Pathway ◽  
Estrogen Signaling ◽  
Control Group ◽  
Noise Induced Hearing Loss ◽  
Sprague Dawley ◽  
Hippocampal Tissue

Although hippocampal changes due to noise-induced hearing loss have been suggested, little is known about the miRNA levels due to these hippocampal changes. Three-week-old Sprague-Dawley rats were divided into noise and control groups ( n = 20 per group). The noise group rats were exposed to white Gaussian noise (115 dB SPL, 4 hours per day) for three days. One day after noise exposure, the hippocampi of rats were harvested and miRNA expressions were analyzed using the Affymetrix miRNA 4.0 microarray ( n = 6 per group). The predicted target genes of each miRNA were retrieved, and the pathways related to the predicted target genes were analyzed. miR-758-5p, miR-210-5p, miR-370-5p, miR-652-5p, miR-3544, miR-128-1-5p, miR-665, miR-188-5p, and miR-874-5p expression increased in the hippocampal tissue of the noise group compared to that in the control group. The overlapping predicted target genes included Bend4, Creb1, Adcy6, Creb5, Kcnj9, and Pten. The pathways related to these genes were the estrogen signaling pathway, vasopressin-regulated water reabsorption, thyroid hormone synthesis, aldosterone synthesis and secretion, insulin secretion, circadian entrainment, insulin resistance, cholinergic synapse, dopaminergic synapse, cGMP-PKG signaling pathway, cAMP signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, and AMPK signaling pathway. miR-448-3p, miR204-5p, and miR-204-3p expression decreased in the hippocampal tissue of the noise group compared to that in the control group. The overlapping predicted target genes of these three miRNAs were Rps6kas, Nfactc3, Rictor, Spred1, Cdh4, Cdh6, Dvl3, and Rcyt1b. Pathway analysis suggested that the Wnt signaling pathway is related to Dvl3 and Nfactc3. Noise-induced hearing loss dysregulates miR-758-5p, miR210-5p, miR370-5p, miR-652-5p, miR-3544, miR-128-1-5p, miR-665, miR-188-5p, miR-874-5p, miR-448-3p, miR-204-5p, miR-204-3p, and miR-140-5p expression in the hippocampus. These miRNAs have been predicted to be associated with hormonal, inflammatory, and synaptic pathways.

scholarly journals The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhuo Wang ◽  
Tingting Zhao ◽  
Shihui Zhang ◽  
Junkai Wang ◽  
Yunyun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Microenvironment ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Target Genes ◽  
Wnt Signaling Pathway ◽  
Systematic Evaluation ◽  
Beta Catenin ◽  
Downstream Target

AbstractWnt signaling was initially recognized to be vital for tissue development and homeostasis maintenance. Further studies revealed that this pathway is also important for tumorigenesis and progression. Abnormal expression of signaling components through gene mutation or epigenetic regulation is closely associated with tumor progression and poor prognosis in several tissues. Additionally, Wnt signaling also influences the tumor microenvironment and immune response. Some strategies and drugs have been proposed to target this pathway, such as blocking receptors/ligands, targeting intracellular molecules, beta-catenin/TCF4 complex and its downstream target genes, or tumor microenvironment and immune response. Here we discuss the roles of these components in Wnt signaling pathway in tumorigenesis and cancer progression, the underlying mechanisms that is responsible for the activation of Wnt signaling, and a series of drugs targeting the Wnt pathway provide multiple therapeutic values. Although some of these drugs exhibit exciting anti-cancer effect, clinical trials and systematic evaluation should be strictly performed along with multiple-omics technology.

Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Rowaida Mohammed Reda M. M Aboushahba ◽  
Fayda Ibrahim Abdel Motaleb ◽  
Ahmed Abdel Aziz Abou-Zeid ◽  
Enas Samir Nabil ◽  
Dalia Abdel-Wahab Mohamed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P < 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

The Pivotal Role of Signal Regulatory Protein α in Exacerbating Pulmonary Fibrosis Complicated with Bacterial Infection

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yamaguchi R ◽  
◽  
Sakamoto A ◽  
Haraguchi M ◽  
Narahara S ◽  
...  
Keyword(s):  
Immune Response ◽  
Pulmonary Fibrosis ◽  
Bacterial Infection ◽  
Signaling Pathway ◽  
Regulatory Protein ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 1 ◽  
Th1 Immune Response

The pathogenesis of pulmonary fibrosis remains unknown. However, bacterial infections in patients with idiopathic pulmonary fibrosis are a serious complication that exacerbate the disease. Serum levels of Surfactant Protein D (SPD) are known to be elevated in patients with pulmonary fibrosis, but the role of SPD in pulmonary fibrosis complicated with bacterial infection is unknown. Lipopolysaccharide upregulates Interleukin (IL)-12p40 expression and IL-12p40 promotes Interferon Gamma (IFNγ) production to induce the T helper cell 1 (Th1) immune response via Signal Transducers and Activators of Transcription 4 (STAT4) signaling. A lack of IFNγ shifts the immune response from Th1 to Th2. IL-4 is a profibrotic Th2 cytokine that activates fibroblasts. Granulocyte-macrophage colony-stimulating factor induced by IL-1 and TNFα during the Th1 immune response upregulates Signal Regulatory Protein α (SIRPα) expression. Interferon Regulatory Factor 1 (IRF1) functions as the promoter activator of IL-12p40 after stimulation with LPS. SPD is a ligand for SIRPα, and SPD/SIRPα ligation activates the Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Related Kinase (ERK) signal cascade; ERK downregulates Interferon Regulatory Factor 1 (IRF1) expression. Consequently, the SPD/SIRPα signaling pathway decreases IL-12p40 production in human macrophages after exposure to LPS. IL-12p40 is a key immunoregulatory factor in bacterial infection that promotes production of IFNγ by T lymphocytes. Pulmonary fibroblasts are activated by IL-4/IL-4R ligation. IFNγ induces IRF1 via STAT1 signaling, and IRF1 acts as the promoter repressor of IL-4 to attenuate its production. IFNγ also inhibits IL-4R expression. A reduction in IFNγ induced by IL-12p40 deficiency via the SPD/SIRPα signaling pathway enhances IL-4 and IL-4R expression to augment the activity of fibroblasts. This finding indicates that pulmonary fibrosis is exacerbated by SPD/SIRPα signaling during bacterial infection.

THE ROLE OF AGONISTS AND ANTAGONISTS OF THE WNT SIGNALING PATHWAY IN PATIENTS WITH ANDROGENIC ALOPECIA AND ALOPECIA AREATA

2021 ◽  
pp. 87-95
Author(s):  
Samoylova A.V. ◽  
Snimshchikova I.A. ◽  
Plotnikova M.O. ◽  
Yakushkina N.Y.
Keyword(s):  
Wnt Signaling ◽  
Hair Follicle ◽  
Signaling Pathway ◽  
Alopecia Areata ◽  
Intracellular Signaling ◽  
Wnt Signaling Pathway ◽  
Follicle Cells ◽  
Androgenic Alopecia ◽  
Active Population

Alopecia is a common pathology among the active population, which leads not only to cosmetic defects, but also to the development of somatic diseases against the background of traumatic effects and chronic stress. The pathogenetic mechanisms of hair follicle formation are complex and diverse, since numerous factors, including the components of the Wnt signaling pathway, have an effect on its morphogenesis, the study of which is the subject of this study. The search for possible early markers of the development of alopecia led to interest in the study of the main morphogenic proteins of WNT - the signaling pathway (one of the intracellular signaling pathways, which control the development of blood vessels, as well as the growth and division of hair follicle cells) sclerostin and β-catenin among patients with androgenic and alopecia areata. The article presents data on the quantitative content of β-catenin and sclerostin in the blood serum in patients with androgenic and alopecia areata. Their possible pathways of complex interaction and influence on the morphogenesis of the hair follicle and the activity of the Wnt-signaling pathway have been analyzed, and the relationship between changes in the level of morphogenic proteins of the WNT-signaling pathway with sex and the course of the disease has been described. Establishment of the prognostic role of morphogenic proteins of the WNT signaling pathway in androgenic and alopecia areata will allow not only identify the personal risk of disease progression and to determine approaches to targeted therapy, but to develop and introduce updated diagnostic screening into dermatological practice.

scholarly journals Analyses of long non-coding RNA and mRNA profiling in the spleen of diarrheic piglets caused by Clostridium perfringens type C

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5997 ◽  
Author(s):  
Zunqiang Yan ◽  
Xiaoyu Huang ◽  
Wenyang Sun ◽  
Qiaoli Yang ◽  
Hairen Shi ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Clostridium Perfringens ◽  
Diarrheal Disease ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Non Coding Rna ◽  
Receptor Signaling Pathway ◽  
Type C ◽  
Long Non Coding Rna

Background Clostridium perfringens (C. perfringens) type C is the most common bacteria causing piglet diarrheal disease and it greatly affects the economy of the global pig industry. The spleen is an important immune organ in mammals; it plays an irreplaceable role in resisting and eradicating pathogenic microorganisms. Based on different immune capacity in piglets, individuals display the resistance and susceptibility to diarrhea caused by C. perfringens type C. Recently, long non-coding RNA (lncRNA) and mRNA have been found to be involved in host immune and inflammatory responses to pathogenic infections. However, little is known about spleen transcriptome information in piglet diarrhea caused by C. perfringens type C. Methods Hence, we infected 7-day-old piglets with C. perfringens type C to lead to diarrhea. Then, we investigated lncRNA and mRNA expression profiles in spleens of piglets, including control (SC), susceptible (SS), and resistant (SR) groups. Results As a result, 2,056 novel lncRNAs and 2,417 differentially expressed genes were found. These lncRNAs shared the same characteristics of fewer exons and shorter length. Bioinformatics analysis identified that two lncRNAs (ALDBSSCT0000006918 and ALDBSSCT0000007366) may be involved in five immune/inflammation-related pathways (such as Toll-like receptor signaling pathway, MAPK signaling pathway, and Jak-STAT signaling pathway), which were associated with resistance and susceptibility to C. perfringens type C infection. This study contributes to the understanding of potential mechanisms involved in the immune response of piglets infected with C. perfringens type C.

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