ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [mRNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA636079 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11881100_1.fastq.gz | Fastqsanger.gz | |||
| SRR11881100_2.fastq.gz | Fastqsanger.gz | |||
| SRR11881101_1.fastq.gz | Fastqsanger.gz | |||
| SRR11881101_2.fastq.gz | Fastqsanger.gz | |||
| SRR11881102_1.fastq.gz | Fastqsanger.gz |
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Project description:Introduction. Hindered by a limited understanding of the molecular mechanisms responsible for diabetic gastroenteropathy (DGE), patients are managed by symptom-based therapies. We investigated the duodenal mucosal expression of protein-coding genes and miRNAs in DGE and related these abnormalities to clinical features. Methods. mRNA and micro RNA (miRNA) expression and ultrastructure of duodenal mucosal biopsies were investigated in 39 DGE patients and 21 healthy controls. Results were analyzed in the context of diabetic phenotype and gastric emptying. Results. There were 3175 differentially-expressed genes (FDR<0.05), especially mitochondrial genes, in DGE versus controls. Several mitochondrial (mt) DNA-encoded genes (12 of 13 protein coding genes mainly involved in oxidative phosphorylation (OXPHOS), both rRNAs and 9 of 22 tRNAs) were downregulated; conversely, nuclear (n) DNA-encoded mitochondrial genes (eg, OXPHOS, TCA cycle) were upregulated in DGE. Motif analysis uncovered binding sites for transcription factors NRF1, GABPA and YY1, which regulate mitochondrial biogenesis, in the promoters of differentially expressed genes. Seventeen of 30 differentially expressed miRNAs in DGE targeted differentially expressed mitochondrial genes. Mitochondrial density was also reduced and correlated with the expression of 9 mt-DNA OXPHOS genes in DGE. Uncovered by a principal component (PC) analysis of OXPHOS genes, PC1 was significantly associated with neuropathy (P = 0.01) and with delayed gastric emptying (P < 0.05). Conclusion. In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased, respectively, associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying, and correlated with cognate miRNA expression. Together, these findings provide substantial evidence for clinically-relevant mitochondrial disturbances in DGE.
2021-03-10 | GSE151496 | GEO
Project description:Introduction. Hindered by a limited understanding of the molecular mechanisms responsible for diabetic gastroenteropathy (DGE), patients are managed by symptom-based therapies. We investigated the duodenal mucosal expression of protein-coding genes and miRNAs in DGE and related these abnormalities to clinical features. Methods. mRNA and micro RNA (miRNA) expression and ultrastructure of duodenal mucosal biopsies were investigated in 39 DGE patients and 21 healthy controls. Results were analyzed in the context of diabetic phenotype and gastric emptying. Results. There were 3175 differentially-expressed genes (FDR<0.05), especially mitochondrial genes, in DGE versus controls. Several mitochondrial (mt) DNA-encoded genes (12 of 13 protein coding genes mainly involved in oxidative phosphorylation (OXPHOS), both rRNAs and 9 of 22 tRNAs) were downregulated; conversely, nuclear (n) DNA-encoded mitochondrial genes (eg, OXPHOS, TCA cycle) were upregulated in DGE. Motif analysis uncovered binding sites for transcription factors NRF1, GABPA and YY1, which regulate mitochondrial biogenesis, in the promoters of differentially expressed genes. Seventeen of 30 differentially expressed miRNAs in DGE targeted differentially expressed mitochondrial genes. Mitochondrial density was also reduced and correlated with the expression of 9 mt-DNA OXPHOS genes in DGE. Uncovered by a principal component (PC) analysis of OXPHOS genes, PC1 was significantly associated with neuropathy (P = 0.01) and with delayed gastric emptying (P < 0.05). Conclusion. In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased, respectively, associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying, and correlated with cognate miRNA expression. Together, these findings provide substantial evidence for clinically-relevant mitochondrial disturbances in DGE.
2021-03-10 | GSE151495 | GEO
Project description:ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY
| PRJNA636083 | ENA
Project description:ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [miRNA-Seq]
| PRJNA636082 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-03-10 | GSE151497 | GEO
Project description:Hindered by a limited understanding of the mechanisms responsible for diabetic gastroenteropathy (DGE), management is symptomatic. We investigated the duodenal mucosal expression of protein-coding genes and microRNAs (miRNA) in DGE and related them to clinical features. The diabetic phenotype, gastric emptying, mRNA, and miRNA expression and ultrastructure of duodenal mucosal biopsies were compared in 39 DGE patients and 21 controls. Among 3175 differentially expressed genes (FDR < 0.05), several mitochondrial DNA-encoded (mtDNA-encoded) genes (12 of 13 protein coding genes involved in oxidative phosphorylation [OXPHOS], both rRNAs and 9 of 22 transfer RNAs) were downregulated; conversely, nuclear DNA-encoded (nDNA-encoded) mitochondrial genes (OXPHOS) were upregulated in DGE. The promoters of differentially expressed genes were enriched in motifs for transcription factors (e.g., NRF1), which regulate mitochondrial biogenesis. Seventeen of 30 differentially expressed miRNAs targeted differentially expressed mitochondrial genes. Mitochondrial density was reduced and correlated with expression of 9 mtDNA OXPHOS genes. Uncovered by principal component (PC) analysis of 70 OXPHOS genes, PC1 was associated with neuropathy (P = 0.01) and delayed gastric emptying (P < 0.05). In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased - associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying - and correlated with cognate miRNAs. These findings suggest that mitochondrial disturbances may contribute to delayed gastric emptying in DGE.
| S-EPMC7934845 | biostudies-literature
Project description:Background. The mechanisms by which environmental risk factors (eg, stress) predispose to symptoms and gastric emptying (GE) disturbances in non-ulcer dyspepsia (NUD) is unknown. Our aims were to compare the circulating leukocytes’ epigenome between NUD patients with normal versus delayed and normal versus rapid GE. Methods. In 24 NUD patients, we evaluated gastrointestinal symptoms, GE (scintigraphy) and 3 promoter/enhancer-associated histone modifications (H3K4me3, H3K9ac, and H3K27ac) by chromatin immunoprecipitation-sequencing in buffy coats, then compared the genome-wide binding of histone marks between patients with normal versus delayed and normal versus rapid GE. Key results. GE was normal (9 patients), delayed (6 patients), or rapid (9 patients). Compared to normal GE, there was differential binding of H3K4me3, which marks active promoters, at 100 genes in delayed and 233 genes in rapid GE (FDR < 0.05). Delayed GE was associated with increased H3K4me3 binding at several genes that regulate T cell functions (eg, CD247, IL2RA, CD69, CD96, ICOS, ITK, and GRAP2); conversely, binding was reduced at genes that regulate neuronal synapses (ie, SYT6, SYT12, CDH2, CDH11, EFNB3, CAMK2B, and SHISA6) and neuronal nitric oxide synthase (NOS1). In rapid GE, genes related to opioid signaling (OPRD1, MAPK4, CAMK2B, and PDE1C), neuronal development, and synaptic functions bound less H3K4me3. No or few genes were differentially enriched with H3K9ac and H3K27ac. Conclusions. H3K4me3 discriminates among patients with normal, rapid, and delayed GE. Delayed GE is associated with alterations that suggest increased T-cell functions. Rapid GE is associated with changes suggesting reduced opioid signaling.
2021-12-26 | GSE139166 | GEO
Project description:OBJECTIVES:Diabetic gastroparesis (Gp) occurs more often in type 1 diabetes mellitus (T1DM) than in type 2 diabetes mellitus (T2DM). Other diabetic end-organ complications include peripheral neuropathy, nephropathy, and retinopathy (together termed triopathy). This study determines the prevalence of diabetic complications (retinopathy, nephropathy, and peripheral neuropathy) in diabetic patients with symptoms of Gp, assessing the differences between T1DM and T2DM and delayed and normal gastric emptying (GE). METHODS:Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy. RESULTS:One hundred thirty-three diabetic patients with symptoms of Gp were studied: 59 with T1DM and 74 with T2DM and 103 with delayed GE and 30 without delayed GE. The presence of retinopathy (37% vs 24%; P = 0.13), nephropathy (19% vs 11%; P = 0.22), and peripheral neuropathy (53% vs 39%; P = 0.16) was not significantly higher in T1DM than in T2DM; however, triopathies (all 3 complications together) were seen in 10% of T1DM and 3% of T2DM (P = 0.04). Diabetic patients with delayed GE had increased prevalence of retinopathy (36% vs 10%; P = 0.006) and number of diabetic complications (1.0 vs 0.5; P = 0.009); however, 39% of diabetic patients with delayed GE did not have any diabetic complications. DISCUSSION:In diabetic patients with symptoms of Gp, delayed GE was associated with the presence of retinopathy and the total number of diabetic complications. Only 10% of patients with T1DM and 3% of those with T2DM had triopathy of complications, and 39% of diabetic patients with Gp did not have any diabetic complications. Thus, the presence of diabetic complications should raise awareness for Gp in either T1DM or T2DM; however, diabetic Gp frequently occurs without other diabetic complications.
| S-EPMC6832848 | biostudies-literature
Project description:Interventions: Group 1: Nicotinell 14mg/24h patch
Group 2: Placebo patch
Primary outcome(s): to assess the effect of transcutaneous administration of nicotine as compared to placebo on the develop-ment and severity of delayed gastric emptying (DGE) following pancreatoduodenectomy
Study Design: Allocation: Randomized controlled study; Masking: Blinded (masking used); Control: placebo; Assignment: parallel; Study design purpose: treatment
| 93375 | ecrin-mdr-crc
Project description:Introduction. Epigenetic modifications have been implicated to mediate several complications of diabetes mellitus (DM), especially nephropathy and retinopathy. Our aims were to ascertain if epigenetic alterations in whole blood discriminate among DM patients with normal, delayed and rapid gastric emptying (GE). Methods. Using ChIP-seq (Chromatin immunoprecipitation combined with next generation sequencing) assays, we compared the genome-wide enrichment of three histone modifications (ie, H3K4me3, H3K9ac and H3K27ac) in buffy coats from 20 DM patients with normal (n=6), delayed (n=8), or rapid (n=6) GE. Results. Between DM patients with delayed versus normal GE, there were 108 and 54 genes that were differentially-bound (FDR < 0.05) with H3K27ac and H3K9ac; 100 genes were differentially bound with H3K9ac in patients with rapid versus normal GE. The differentially bound genes with H3K27ac were functionally linked to the type 2 immune response, particularly Th2 cell activation and function (eg, CCR3, CRLF2, CXCR4, IL5RA, and IL1RL1) and glucose homeostasis (FBP-1, PDE4A, CMKLR1). For H3K9ac, the differentially occupied genes were related to T cell development and function (eg, ICOS and CCR3) and innate immunity (RELB, CD300LB, CLEC2D). Compared to normal, rapid GE had differential H3K9ac peaks at the promoter site of diverse immunity-related genes (eg, TNFRSF25 and CXCR4) and genes related to insulin resistance and glucose metabolism. The motif analysis disclosed enrichment of binding sites for several transcription factors relevant to the pathogenesis and complications of DM. Conclusions. GE disturbances in DM are associated with epigenetic alterations that may serve as biomarkers and provide clues to the pathogenesis
2021-12-26 | GSE142178 | GEO