Gene expression profiling of sciatic nerves from rats with diabetic peripheral neuropathy
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ABSTRACT:
PROVIDER: PRJNA616271 | ENA |
REPOSITORIES: ENA
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Project description:To identify the key genes and pathways which might play critical roles in the pathogenesis of experimental DPN via microarray analysis. Adult male Sprague-Dawley rats (initial weight 250-300g, from the department of laboratory animal science of Fudan University) were randomly assigned into two groups: control rats and diabetic rats. Diabetes was induced with a single intraperitoneal injection of STZ (55mg/kg). Control rats were performed with a single intraperitoneal injection of 0.9% saline solution. Glucose level was evaluated using Sannuo strips on tail vein blood at day 3 after STZ injection and verified again at day 7 after STZ injection. Only rats with blood glucose level 16.7 mmol/L were considered diabetic.Six weeks after diabetes induction, nerve tissue samples (about 1cm long) were harvested from the right sciatic nerve of rats in control (n=3) and diabetic (n=3) groups for total RAN isolation. Microarray hybridization was then performed according to the Agilent One-Color Microarray-Based Gene Expression Analysis protocol (Agilent Technologies). Quantile normalization and subsequent data processing were performed using the GeneSpring GX v12.1 software package (Agilent Technologies). The univariate t-test with a fold-change >2 and P value < 0.001 was applied to identify the DEGs between control rats and diabetic rats. Credibility of the microarray data was validated through qRT-PCR on 4 genes. Total RNA was independently extracted from the right sciatic nerve of rats in both groups (n=3) 6 weeks after diabetes induction.
2020-03-31 | GSE147732 | GEO
Project description:Female mouse models of diabetic peripheral neuropathy (DPN) have not yet been identified. Our aim is firstly to demonstrate that female BTBR ob/ob mice display robust DPN and secondly, to perform relevant comparisons with non-diabetic and gender-matched controls. Lastly, microarray technology was employed to identify dysregulated genes and pathways in the SCN and DRG of female BTBR mice. Dorsal root ganglia (DRG) and sciatic nerve (SCN) were removed from female mice, RNA isolated and processed for gene expression profiling to identify differentially expressed genes using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays.
2016-07-12 | GSE70852 | GEO
Project description:The mechanisms of diabetic neuropathy (DN) development and progression are not fully understood. We examined global gene expression in the sciatic nerve (SCN) of BKS-db/db mice at 8 and 24 weeks of age to identify genetic pathways altered in peripheral nerves at early and advanced stages of DN. The sets of differentially expressed genes were analyzed to identify enriched biological functions and regulated genetic pathways. Our results suggest that carbohydrate metabolism and lipid metabolism pathways are dysregulated in the db/db SCN at 8 weeks of age. Impairment of Schwann cell-extracellular matrix interaction and axon guidance occurs early in the development of DN, while neurotrophic support, neurotransmitter transport and axonogenesis are impaired at the advanced stage of DN. Gene expression changes also suggest that oxidative stress- and inflammation-mediated nerve damage occurs by 8 weeks. Our analysis identified mechanisms regulated in the early stages of DN. Additionally, interactions between genes from different pathways provide insight into potential relationships among the regulated pathways.
2012-01-06 | GSE34889 | GEO
Project description:The mechanisms of diabetic neuropathy (DN) development and progression are not fully understood. We examined global gene expression in the sciatic nerve (SCN) of BKS-db/db mice at 8 and 24 weeks of age to identify genetic pathways altered in peripheral nerves at early and advanced stages of DN. The sets of differentially expressed genes were analyzed to identify enriched biological functions and regulated genetic pathways. Our results suggest that carbohydrate metabolism and lipid metabolism pathways are dysregulated in the db/db SCN at 8 weeks of age. Impairment of Schwann cell-extracellular matrix interaction and axon guidance occurs early in the development of DN, while neurotrophic support, neurotransmitter transport and axonogenesis are impaired at the advanced stage of DN. Gene expression changes also suggest that oxidative stress- and inflammation-mediated nerve damage occurs by 8 weeks. Our analysis identified mechanisms regulated in the early stages of DN. Additionally, interactions between genes from different pathways provide insight into potential relationships among the regulated pathways. RNA extracted from the SCN of four groups of mice: (8 week old db/db (n=8) or db/+ (n=8), and 24 week old db/db (n=6) or db/+ (n=7)) was hybridized to Affymetrix GeneChip microarrays. Gene expression for the two genotypes (db/db vs. db/+) was compared at each age. Gene expression at the early and advanced stages of DN (8 weeks vs. 24 weeks) was also compared for each genotype.
2012-01-06 | E-GEOD-34889 | biostudies-arrayexpress
Project description:To investigate the potential function of lncRNAs in Schwann cell (SCs) response to sciatic nerve damage and repair, we extracted the total RNA of crushed sciatic nerves and intact contralateral nerves for RNA-sequencing (RNA-seq). A total of 98 differentially expressed lncRNAs (including 46 up-regulated and 52 down-regulated lncRNAs) and 77 differentially expressed mRNAs (including 55 up-regulated and 22 down-regulated mRNAs) were identified between crushed sciatic nerves and normal control (log 2 FC > 1 and p < 0.001).
2022-07-06 | GSE149657 | GEO
Project description:Immune cells infiltrate peripheral nerves after injury and with autoimmunity, but their net effect is divergent. After injury, immune cells are reparative, while in autoimmune neuropathies (e.g., GBS and CIDP), immune cells are pro-inflammatory and promote autoimmune demyelination. An understanding of immune cell phenotypes that distinguish these conditions may therefore reveal new therapeutic targets for switching immune cells from an inflammatory to a reparative state. In an autoimmune neuropathy mouse model, we used single cell transcriptomic studies of sciatic nerves to discover a TNFα signaling axis induced by IFNγ. Macrophages were the main source of TNFα, and autocrine TNFα signaling upregulated multiple autoimmunity-associated genes (e.g., Clec4e; Marcksl1; Cxcl1; Cxcl10). TNFα signaling was absent in nerve macrophages after injury, suggesting that TNFα signaling defines autoimmunity-associated pro-inflammatory macrophages. Finally, TNFα/TNFα signaling blockade ameliorated PNS autoimmunity development, which provides pre-clinical evidence that the TNFα axis may be effectively targeted to resolve inflammatory neuropathies.
2021-11-30 | GSE180498 | GEO
Project description:We performed gene expression pofiling of Zeb2cKO and control sciatic nerves and identified significantly changed genes ZEB2 is also known as SIP1 4 RNA-Seq samples from P7 sciatic nerves of Ctrl and Zeb2 cKO mice (duplicatess, Ctrl and cKO)
2016-06-13 | E-GEOD-74381 | biostudies-arrayexpress
Project description:The transcriptome of sciatic nerves was investigated by RNA sequencing. We compared the transcriptome of ZH3 sciatic nerves to WT sciatic nerves in two age groups. Differentially expressed genes were considered as indicators of peripheral nerve damage in ZH3 mice. Then, we compared the sciatic nerve transcriptome of ZH3 mice chronically treated with a dimeric PrP-fusion protein (FT2Fc) to the two control groups treated with either buffer or mouse IgG. This comparison revealed specific changes induced by FT2Fc treatment. Contrary to our hypothesis, FT2Fc treatment did not alter the expression of the genes that were dysregulated in young and old ZH3 mice (as identified in the first part of the study).
2020-10-29 | GSE159948 | GEO
Project description:Guillain-Barré syndrome (GBS) is characterized by acute immune-mediated peripheral neuropathy, which may result in rapidly progressive paralysis and fatal respiratory failure. As the underlying pathological mechanisms of GBS are unclear, we surveyed the transcriptome of rats with experimental autoimmune neuritis (EAN), a model of GBS. Briefly, sciatic nerves on both sides were collected from 8–10-week-old Lewis rats during early (10 days post-induction), peak (19 days), and late neuritis (30 days). Total RNA was sequenced to identify differentially expressed genes. Compared to control rats without induced neuritis, 33 genes were differentially expressed in the early phase (14 upregulated and 19 downregulated), with an adjusted P-value < 0.05 and |log2 fold-change| > 1, as were 137 genes in the peak phase (126 upregulated and 11 downregulated) and 60 genes in the late phase (58 upregulated and 2 downregulated). Eleven of these genes were common to all stages, suggesting their crucial roles throughout the disease course. Analysis of protein-protein interactions revealed Fos, Ccl2, Itgax and C3 as node genes at different stages. Functional analysis of differentially expressed genes identified biological processes and pathways that are activated as neuritis progresses. This is the first genome-wide gene expression study of peripheral nerves in experimental autoimmune neuritis model. Dynamic gene expression and significantly altered biological functions were detected in different phases of the disease, increasing our understanding of the molecular mechanisms underlying EAN and highlighting potential targets for its diagnosis and treatment.
2020-01-22 | GSE133750 | GEO
Project description:The objective of this study was to determine which pathways are significantly regulated with age in sciatic and radial nerves, individually or considering the interaction term. We find a strong signature of the cholesterol biosynthesis pathway being downregulated with age in both nerves, however, this effect is significantly milder in the radial nerve. We collected both radial and sciatic nerves from 8 adult (8 months old) and 8 old (24 months old) rats.
2016-05-12 | E-GEOD-77022 | biostudies-arrayexpress