Dataset Information

Molecular Mechanisms Underlying Intestinal Ischemia/Reperfusion Injury: Bioinformatics Analysis and In Vivo Validation.

ABSTRACT: BACKGROUND Intestinal ischemia/reperfusion (I/R) injury is a serious clinical complication. This study aimed to explore the hub genes and pathways of intestinal I/R injury. MATERIAL AND METHODS GSE96733 from the GEO website was extracted to analyze the differentially expressed genes (DEGs) of intestinal I/R injured and sham-operated mice at 3 h and 6 h after surgery. The DAVID and STRING databases were used to construct functional enrichment analyses of DEGs and the protein-protein interaction (PPI) network. In Cytoscape software, cytoHubba was used to identify hub genes, and MCODE was used for module analysis. Testing by qRT-PCR detected the expression of hub genes in intestinal I/R injury. Western blot analysis detected the key proteins involved with the important pathways of intestinal I/R injury. RESULTS IL-6, IL-10, CXCL1, CXCL2, and IL-1ß were identified as critical upregulated genes, while IRF7, IFIT3, IFIT1, Herc6, and Oasl2 were identified as hub genes among the downregulated genes. The qRT-PCR testing showed the expression of critical upregulated genes was significantly increased in intestinal I/R injury (P<0.05), while the expression of hub downregulated genes was notably reduced (P<0.05). The proteins of CXCL1 and CXCR2 were upregulated following intestinal I/R injury (P<0.05) and the CXCL1/CXCR2 axis was involved with intestinal I/R injury. CONCLUSIONS The results of the present study identified IL-6, IL-10, CXCL1, CXCL2, IL-1ß, IRF7, IFIT3, IFIT1, Herc6, and Oasl2 as hub genes in intestinal I/R injury and identified the involvement of the CXCL1/CXCR2 axis in intestinal I/R injury.

SUBMITTER: Chen F

PROVIDER: S-EPMC7733309 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular Mechanisms Underlying Intestinal Ischemia/Reperfusion Injury: Bioinformatics Analysis and In Vivo Validation.

Chen Fengshou F Wang Dan D Li Xiaoqian X Wang He H

Medical science monitor : international medical journal of experimental and clinical research 20201208

BACKGROUND Intestinal ischemia/reperfusion (I/R) injury is a serious clinical complication. This study aimed to explore the hub genes and pathways of intestinal I/R injury. MATERIAL AND METHODS GSE96733 from the GEO website was extracted to analyze the differentially expressed genes (DEGs) of intestinal I/R injured and sham-operated mice at 3 h and 6 h after surgery. The DAVID and STRING databases were used to construct functional enrichment analyses of DEGs and the protein-protein interaction ( ...[more]

PMID: 33290384

Similar Datasets

Project description:Intestinal ischemia-reperfusion (I/R) injury is a devastating complication when the blood supply is reflowed in ischemic organs. Gastrin has critical function in regulating acid secretion, proliferation, and differentiation in the gastric mucosa. We aimed to determine whether gastrin has an effect on intestinal I/R damage. Intestinal I/R injury was induced by 60-min occlusion of the superior mesenteric artery followed by 60-min reperfusion, and the rats were induced to be hypergastrinemic by pretreated with omeprazole or directly injected with gastrin. Some hypergastrinemic rats were injected with cholecystokinin-2 (CCK-2) receptor antagonist prior to I/R operation. After the animal surgery, the intestine was collected for histological analysis. Isolated intestinal epithelial cells or crypts were harvested for RNA and protein analysis. CCK-2 receptor expression, intestinal mucosal damage, cell apoptosis, and apoptotic protein caspase-3 activity were measured. We found that high gastrin in serum significantly reduced intestinal hemorrhage, alleviated extensive epithelial disruption, decreased disintegration of lamina propria, downregulated myeloperoxidase activity, tumor necrosis factor-?, and caspase-3 activity, and lead to low mortality in response to I/R injury. On the contrary, CCK-2 receptor antagonist L365260 could markedly impair intestinal protection by gastrin on intestinal I/R. Severe edema of mucosal villi with severe intestinal crypt injury and numerous intestinal villi disintegrated were observed again in the hypergastrinemic rats with L365260. The survival in the hypergastrinemic rats after intestinal I/R injury was shortened by L365260. Finally, gastrin could remarkably upregulated intestinal CCK-2 receptor expression. Our data suggest that gastrin by omeprazole remarkably attenuated I/R induced intestinal injury by enhancing CCK-2 receptor expression and gastrin could be a potential mitigator for intestinal I/R damage in the clinical setting.

Project description:Spinal cord ischemia-reperfusion injury (SCII) is a pathological process with severe complications such as paraplegia and paralysis. Aberrant miRNA expression is involved in the development of SCII. Differences in the experimenters, filtering conditions, control selection, and sequencing platform may lead to different miRNA expression results. This study systematically analyzes the available SCII miRNA expression data to explore the key differently expressed miRNAs (DEmiRNAs) and the underlying molecular mechanism in SCII. A systematic bioinformatics analysis was performed on 23 representative rat SCII miRNA datasets from PubMed. The target genes of key DEmiRNAs were predicted on miRDB. The DAVID and TFactS databases were utilized for functional enrichment and transcription factor binding analyses. In this study, 19 key DEmiRNAs involved in SCII were identified, 9 of which were upregulated (miR-144-3p, miR-3568, miR-204, miR-30c, miR-34c-3p, miR-155-3p, miR-200b, miR-463, and miR-760-5p) and 10 downregulated (miR-28-5p, miR-21-5p, miR-702-3p, miR-291a-3p, miR-199a-3p, miR-352, miR-743b-3p, miR-125b-2-3p, miR-129-1-3p, and miR-136). KEGG enrichment analysis on the target genes of the upregulated DEmiRNAs revealed that the involved pathways were mainly the cGMP-PKG and cAMP signaling pathways. KEGG enrichment analysis on the target genes of the downregulated DEmiRNAs revealed that the involved pathways were mainly the Chemokine and MAPK signaling pathways. GO enrichment analysis indicated that the target genes of the upregulated DEmiRNAs were markedly enriched in biological processes such as brain development and the positive regulation of transcription from RNA polymerase II promoter. Target genes of the downregulated DEmiRNAs were mainly enriched in biological processes such as intracellular signal transduction and negative regulation of cell proliferation. According to the transcription factor analysis, the four transcription factors, including SP1, GLI1, GLI2, and FOXO3, had important regulatory effects on the target genes of the key DEmiRNAs. Among the upregulated DEmiRNAs, miR-3568 was especially interesting. While SCII causes severe neurological deficits of lower extremities, the anti-miRNA oligonucleotides (AMOs) of miR-3568 improve neurological function. Cleaved caspase-3 and Bax was markedly upregulated in SCII comparing to the sham group, and miR-3568 AMO reduced the upregulation. Bcl-2 expression levels showed a opposite trend as cleaved caspase-3. The expression of GATA6, GATA4, and RBPJ decreased after SCII and miR-3568 AMO attenuated this upregulation. In conclusion, 19 significant DEmiRNAs in the pathogenesis of SCII were identified, and the underlying molecular mechanisms were validated. The DEmiRNAs could serve as potential intervention targets for SCII. Moreover, inhibition of miR-3568 preserved hind limb function after SCII by reducing apoptosis, possibly through regulating GATA6, GATA4, and RBPJ in SCII.

Dataset Information

Molecular Mechanisms Underlying Intestinal Ischemia/Reperfusion Injury: Bioinformatics Analysis and In Vivo Validation.

Publications

Molecular Mechanisms Underlying Intestinal Ischemia/Reperfusion Injury: Bioinformatics Analysis and In Vivo Validation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets