Quantitative transcriptome analysis of the repair mechanism of AKBA on the treatment of rat sciatic nerve injury
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE179400 | GEO | 2022/06/23
REPOSITORIES: GEO
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Project description:Background: Although clinical outcome of arteriovenous fistula (AVF) as a preferred vascular access for hemodialysis has been inadequate, biological mechanisms of AVF maturation and failure is still poorly understood. Since our mouse AVF model recapitulates human AVF maturation and partial failure, we hypothesized that high throughput RNA sequencing (RNA-seq) analysis would identify early changes in gene expression that might predict AVF maturation and failure. Method: Aortocaval fistula creation (AVF group) or sham operation (sham group) was performed with C57BL/6 mice (10 wk). Ultrasound was performed to confirm the AVF patency and to measure hemodynamics. Venous limbs were collected on postoperative day 7 and total RNA was extracted. After Poly-A mRNA libraries were constructed, RNA-seq was performed. Differentially expressed genes (DEG) were identified, and subsequent enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed with bioinformatics techniques. Results: 1057 DEG were identified between the AVF and sham groups. Genes in metabolic pathways were significantly downregulated in the AVF. Since gene expression patterns among the AVF group were significantly heterogenous, the AVF group was divided into 2 groups (‘normal’ AVF group; nAVF and ‘outliers’ group; OUT), and subgroup analyses were performed. Although physiological data of body weight change and hemodynamics were not different between the nAVF and OUT groups, 413 DEG were identified between them. Enrichment analyses showed significant overrepresentation of metabolism, immunity, and coagulation in the OUT group. Comparing the nAVF group with the sham group, 403 DEG were identified. Enrichment analyses showed increase of gene expression related to cell cycle, extracellular matrix, and immunity. Comparing these results with previously published data, the gene expression patterns of the nAVF group was consistent with AVF maturation and adaptive remodeling, whereas the OUT group showed attenuated difference, suggesting the heterogeneity of the AVF group reflects early gene expression changes in the process of AVF maturation and failure. Significant sex differences were not observed in the AVF group. Conclusions: A small subset of AVF undergoes aberrant biological processes in the early phase including diminished ECM remodeling, activated coagulation and upregulated metabolism, that could lead to fistula failure. Detection of these processes might be a viable translational strategy to predict fistula failure and reduce patient morbidity.
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Project description:We reported the RNAseq analyses of right ventricualr free wall myocardium in young volume overload (VO) C57/BL6 mice.VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) on postnatal day 7(P7). RNAseq analyses of RV free wall at P14 and P21from VO and sham-operated mice revealed that there were 981 differentially expressed genes between VO and sham group at P14, this number increased to 1907 at P21, there were 3012 differentially expressed genes between P21 and P14 sham group, and the number increased to 3470 at the presence of VO. GO analysis showed that in the VO and sham comparison, the upregulated genes mainly mediated mitosis and cell division and the downregulated genes mainly mediated heart contraction at P14, and the upregulated genes mainly mediated immune response, and downregulated genes mainly mediated cellular respiration at P21. As expected, in the normal RV development during preadolescence (from P14 to P21), upregulated genes mainly mediated oxidative phosphorylation and cellular respiration and the downregulated genes mainly mediated vasculogenesis. VO changed the RV development, the upregulated genes mainly mediated heart contraction and the down regulated genes mainly mediated vasculogenesis and cell cycle. KEGG pathway analysis revealed that cell cycle pathway was upregulated and cardiac muscle contraction and thyroid hormone signaling pathway were downregulated between VO and sham group at P14, phagosome pathway was upregulated and citrate cycle (TCA) cycle and thermogenesis were downregulated at P21 between VO and sham group. In the normal RV development, TCA cycle and cardiac muscle contraction pathway were upregulated while VO changed that to the upregulations of cardiomyopathy pathways and thyroid hormone signaling pathway. All the above changes were further confirmed by the functional tests.
2021-08-16 | GSE157396 | GEO
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Project description:Comparing the effect of unilateral ischemia-reperfusion injury (IRI) or sham operation (sIRI) with delayed contralateral nephrectomy (Nx) or sham operation (sNx) in mouse kidney. IRI was performed on day 0 and the contralateral kidney was removed on day 7. Mice were sacrificed on day 8. Four animals were selected from the sham IRI-sham Nx and sham IRI-Nx groups and six animals were selected from the IRI-sham Nx and IRI-Nx groups for miRNA microArray analysis on the base of their proinflammatory (TNF-α and IL-6 and CCL2) and immune system-related (Complement component 3) mRNA expression levels.
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Project description:We obtained the profiles of neuronal proteome after cerebral ischemia and reperfusion by isolating mice hippocampus. Hippocampus combined from either nine sham or nine focal cerebral ischemia 1.5 h and reperfusion 24 h (IR) mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. In total, we quantified 5,059 proteins. We identified 142 differentially expressed proteins (t-test, p-value<0.05) after IR compared to sham groups. The results showed that 92 proteins were upregulated, and 50 proteins were downregulated after IR compared to sham groups. Gene ontology (GO) enrichment analysis of differentially expressed proteins between sham and IR groups. The results showed that the biological process of most of upregulated genes linked with immune inflammatory related responses were increased. And KEGG pathway analysis for upregulated genes showed that multiple immune inflammatory response pathways also increased significantly, such as TNF-signaling, NF-κB signaling and cytokine-cytokine receptor interaction, as well as NOD-like receptor signaling, and toll-like receptor signaling.
2024-02-15 | PXD033938 | Pride
Project description:Purpose: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the key genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats. Methods: Three-month-old female Sprague–Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX+EX) group. The OVX+EX group performed moderate-intensity treadmill exercise for 17 weeks. Upon completion of these exercises, the body composition and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry, and the bone microstructure of the femur was observed using micro-computed tomography scanning. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing. The Metascape software was used for gene ontology and pathway enrichment analysis to further screen key genes. Results: 1. In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group and the body muscle content and BMD were significantly lower. 2. The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX+EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, the trabecular bones were sparse, and there was a large gap between the trabecular bones. The number and continuity of the trabecular bones were higher in OVX+EX group than in the OVX group. 3. A Venn diagram showed that there were 58 common differential genes, with a fold change ≥2 and p value <0.05. and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five key genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The results also showed that the PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis.
2021-11-17 | GSE184493 | GEO
Project description:We obtained the profiles of neuronal phosphoproteome after cerebral ischemia onset by isolating mice hippocampus. Hippocampus combined from either ten sham or ten focal cerebral ischemia 2 h mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. Five percent of the pool was used for whole proteome analysis, and the remaining 95% was subjected to phosphoproteome profiling. In total, we quantified 5,174 proteins and 9,062 phosphopeptides. Interesting, 21 proteins were upregulated and 7 proteins were downregulated in hippocampus lysates of cerebral ischemia 2 h relative to sham base on fold change. S100a9, Alpha-2-HS-glycoprotein (Ahsg), Fibrinogen beta chain (Fga) and Complement Component C3(c3) are the top significantly changed, which were highly consistent with previous reports in cerebral ischemia injury. Using wolfpsort software to analysis the Subcellular Location, 57% of detected proteins were location to extracellular, 15% were cytoplasmic protein, another 11% were transport to nucleus, and the others were location to plasma membranes (10%), mitochondria (4%) and endoplasmic reticulum (3%). Moreover,184 phosphorylation sites of 135 proteins were upregulated and 689 phosphorylation sites of 420 proteins were downregulated in hippocampus during cerebral ischemia 2 h compare with sham operation. Employing wolfpsort software analysis the subcellular location, 50% of phosphorylated proteins were location to nucleus, 26% were cytoplasmic protein, another 16% were transport to plasma membranes, and the others were location to mitochondria (4%), extracellular (3%) and cytoskeleton (1%). Motif analysis showed that 85% were belongs to serine-type phosphorylation, about 14 were threonine-type phosphorylation and 1% were tyrosine-type phosphorylation.
2022-03-14 | PXD027145 | Pride