scholarly journals Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury

2021 ◽  
Vol 22 (21) ◽  
pp. 11601
Author(s):  
Eun-Jung Sohn ◽  
Yun-Kyeong Nam ◽  
Hwan-Tae Park
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathway ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Target Genes ◽  
Adenosine Monophosphate ◽  
Cell Phenotype ◽  
Pathway Enrichment Analysis ◽  
Guanine Nucleotide Binding Protein ◽  
Calcium Signaling Pathway

Although microRNAs (miRNAs or miRs) have been studied in the peripheral nervous system, their function in Schwann cells remains elusive. In this study, we performed a microRNA array analysis of cyclic adenosine monophosphate (cAMP)-induced differentiated primary Schwann cells. KEGG pathway enrichment analysis of the target genes showed that upregulated miRNAs (mR212-5p, miR335, miR20b-5p, miR146b-3p, and miR363-5p) were related to the calcium signaling pathway, regulation of actin cytoskeleton, retrograde endocannabinoid signaling, and central carbon metabolism in cancer. Several key factors, such as purinergic receptors (P2X), guanine nucleotide-binding protein G(olf) subunit alpha (GNAL), P2RX5, P2RX3, platelet-derived growth factor receptor alpha (PDGFRA), and inositol 1,4,5-trisphosphate receptor type 2 (ITPR2; calcium signaling pathway) are potential targets of miRNAs regulating cAMP. Our analysis revealed that miRNAs were differentially expressed in cAMP-treated Schwann cells; miRNA363-5p was upregulated and directly targeted the P2X purinoceptor 4 (P2RX4)-UTR, reducing the luciferase activity of P2RX4. The expression of miRNA363-5p was inhibited and the expression of P2RX4 was upregulated in sciatic nerve injury. In contrast, miRNA363-5p expression was upregulated and P2RX4 expression was downregulated during postnatal development. Of note, a P2RX4 antagonist counteracted myelin degradation after nerve injury and increased pERK and c-Jun expression. Interestingly, a P2RX4 antagonist increased the levels of miRNA363-5p. This study suggests that a double-negative feedback loop between miRNA363-5p and P2RX4 contributes to the dedifferentiation and migration of Schwann cells after nerve injury.

scholarly journals Calcium Signaling Alterations Caused by Epigenetic Mechanisms in Pancreatic Cancer: From Early Markers to Prognostic Impact

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1735 ◽  
Author(s):  
Cleandra Gregório ◽  
Sheila Coelho Soares-Lima ◽  
Bárbara Alemar ◽  
Mariana Recamonde-Mendoza ◽  
Diego Camuzi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Calcium Signaling ◽  
Signaling Pathway ◽  
Tumor Biology ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Pathway Enrichment Analysis ◽  
Prognostic Impact ◽  
Phenotypic Effect ◽  
Calcium Signaling Pathway

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high mortality rates. PDAC initiation and progression are promoted by genetic and epigenetic dysregulation. Here, we aimed to characterize the PDAC DNA methylome in search of novel altered pathways associated with tumor development. We examined the genome-wide DNA methylation profile of PDAC in an exploratory cohort including the comparative analyses of tumoral and non-tumoral pancreatic tissues (PT). Pathway enrichment analysis was used to choose differentially methylated (DM) CpGs with potential biological relevance. Additional samples were used in a validation cohort. DNA methylation impact on gene expression and its association with overall survival (OS) was investigated from PDAC TCGA (The Cancer Genome Atlas) data. Pathway analysis revealed DM genes in the calcium signaling pathway that is linked to the key pathways in pancreatic carcinogenesis. DNA methylation was frequently correlated with expression, and a subgroup of calcium signaling genes was associated with OS, reinforcing its probable phenotypic effect. Cluster analysis of PT samples revealed that some of the methylation alterations observed in the Calcium signaling pathway seemed to occur early in the carcinogenesis process, a finding that may open new insights about PDAC tumor biology.

scholarly journals The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yinjie Gao ◽  
Xiaosen Ma ◽  
Huiping Wang ◽  
Yunying Cui ◽  
Yushi Zhang ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathway ◽  
Quantitative Pcr ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Differentially Expressed Gene ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Mrna Levels ◽  
Calcium Signaling Pathway

Purpose. Previous studies have investigated the transcriptional modulations of aldosterone overproduction of aldosterone-producing adenomas (APAs). We aimed to systematically study the genes and pathways associated with molecular mechanism underlying APA by bioinformatics analysis and experimental validation for the expression profile. Methods. This study was performed based on three gene expression profiles (GSE64957, GSE8514, and GSE60042). Differentially expressed gene (DEG) investigation, function and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed by the bioinformatics analysis. For the validation with quantitative PCR, tissues from 11 patients with nonfunctioning adrenal adenoma (NFA) and 13 with APA were included in our cohort. Results. In this study, the bioinformatics analysis was performed and 182 upregulated and 88 downregulated DEGs were identified. As expected, the upregulated DEGs were primarily involved in calcium ion homeostasis ( p  = 2.00X10−4). In the KEGG pathway analysis, calcium signaling pathway ( p  = 4.38X10−6) and the aldosterone synthesis and secretion ( p  = 8.73X10−6) were enriched. Moreover, quantitative PCR was performed to detect the expression of 7 upregulated genes (PCP4, ATP2A3, CYP11B2, CLCN5, HTR4, VDR, and AQP2) among the intersection of DEGs. The mRNA levels of CYP11B2, HTR4, and AQP2 were significantly increased in APA samples compared to NFA (24.420 folds of NFA, p  < 0.001; 3.753 folds of NFA, p  = 0.002; and 11.487 folds of NFA, p  = 0.018). Conclusion. In summary, the present study showed several candidate genes with high expression from bioinformatics analysis and our cohort. Also, the DEGs were enriched in aldosterone synthesis and secretion and calcium signaling pathway as expected.

scholarly journals Localization of the Cyclic ADP-ribose-dependent Calcium Signaling Pathway in Hepatocyte Nucleus

2000 ◽  
Vol 275 (32) ◽  
pp. 24807-24817 ◽  
Author(s):  
Keng Meng Khoo ◽  
Myung-Kwan Han ◽  
Jin Bong Park ◽  
Soo Wan Chae ◽  
Uh-Hyun Kim ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathway ◽  
Hepatocyte Nucleus ◽  
Calcium Signaling Pathway ◽  
Cyclic Adp Ribose

Paeoniflorin inhibits MRGPRX2‐mediated pseudo‐allergic reaction via calcium signaling pathway

2019 ◽  
Vol 34 (2) ◽  
pp. 401-408
Author(s):  
Jianli Wang ◽  
Yongjing Zhang ◽  
Jue Wang ◽  
Rui Liu ◽  
Guiping Zhang ◽  
...  
Keyword(s):  
Allergic Reaction ◽  
Calcium Signaling ◽  
Signaling Pathway ◽  
Calcium Signaling Pathway

scholarly journals Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Mengshi Tang ◽  
Xi Xie ◽  
Pengji Yi ◽  
Jin Kang ◽  
Jiafen Liao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Binding Activity ◽  
New Combination ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Potential Mechanism

Objective. To explore the main components and unravel the potential mechanism of simiao pill (SM) on rheumatoid arthritis (RA) based on network pharmacological analysis and molecular docking. Methods. Related compounds were obtained from TCMSP and BATMAN-TCM database. Oral bioavailability and drug-likeness were then screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Additionally, target genes related to RA were acquired from GeneCards and OMIM database. Correlations about SM-RA, compounds-targets, and pathways-targets-compounds were visualized through Cytoscape 3.7.1. The protein-protein interaction (PPI) network was constructed by STRING. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via R packages. Molecular docking analysis was constructed by the Molecular Operating Environment (MOE). Results. A total of 72 potential compounds and 77 associated targets of SM were identified. The compounds-targets network analysis indicated that the 6 compounds, including quercetin, kaempferol, baicalein, wogonin, beta-sitosterol, and eugenol, were linked to ≥10 target genes, and the 10 target genes (PTGS1, ESR1, AR, PGR, CHRM3, PPARG, CHRM2, BCL2, CASP3, and RELA) were core target genes in the network. Enrichment analysis indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. Molecular docking showed that quercetin, kaempferol, baicalein, and wogonin have good binding activity with IL6, VEGFA, EGFR, and NFKBIA targets. Conclusion. The integrative investigation based on bioinformatics/network topology strategy may elaborate on the multicomponent synergy mechanisms of SM against RA and provide the way out to develop new combination medicines for RA.

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