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ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [miRNA-Seq]

ABSTRACT: ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [miRNA-Seq]

PROVIDER: PRJNA636082 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11881132_1.fastq.gz	Fastqsanger.gz
	SRR11881132_2.fastq.gz	Fastqsanger.gz
	SRR11881133_1.fastq.gz	Fastqsanger.gz
	SRR11881133_2.fastq.gz	Fastqsanger.gz
	SRR11881134_1.fastq.gz	Fastqsanger.gz

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ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [miRNA-Seq]

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

ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [mRNA-Seq]

2021-03-10 | GSE151495 | GEO

ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY

Project description:ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY

| PRJNA636083 | ENA

ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [mRNA-Seq]

Project description:ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [mRNA-Seq]

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ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-10 | GSE151497 | GEO

Duodenal mucosal mitochondrial gene expression is associated with delayed gastric emptying in diabetic gastroenteropathy.

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

Duodenal Mucosal Barrier in Functional Dyspepsia

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Duodenal Mucosal Barrier in Functional Dyspepsia [miRNA]

Project description:Epithelial Barrier and Leaky Gut in Dyspepsia Running title: Epithelial Barrier and Leaky Gut in Dyspepsia Context: Some studies suggest that FD is associated with ex vivo duodenal epithelial micro-inflammation and barrier impairment; the pathogenesis of these findings is unclear. miRNAs reduce expression of epithelial barrier genes and have been postulated to increase epithelial permeability in irritable bowel syndrome. New findings: Compared to controls, there is reduced mRNA expression of several barrier proteins (zona occludin-1), increased expression of several miRNAs (eg, miR-142-3p) that suppress the genes for barrier proteins in FD. However, mucosal eosinophils, intraepithelial lymphocytes, and mast cells, ex- and in vivo permeability (urinary lactulose and mannitol excretion) were not significantly different in FD. Impact: Patients with FD do not have a leaky gut syndrome.

2023-03-01 | GSE169307 | GEO

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