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Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

ABSTRACT: Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

PROVIDER: PRJNA540941 | ENA |

REPOSITORIES: ENA

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Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

Project description:Background: Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in animal models of diabetes. Human studies have also revealed loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages in full thickness gastric biopsies from gastroparesis patients. Aim: We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in full thickness gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying and symptoms. Methods: Full-thickness gastric antrum biopsies were obtained from nine DG, seven IG patients and five non-diabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1300 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity Pathway Analysis and correlations were carried out. Multiple-testing corrected p-values <0.05 were considered statistically significant. Results: 73 proteins were differentially expressed in DG, 132 proteins in IG and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway (DG FDR: 7.9x10-9; IG FDR: 6.3x10-12). In DG, properdin expression correlated with GCSI-bloating (r: -0.99, FDR: 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C zeta type and complement C2 correlated with 4 hr gastric retention (r: -0.97, FDR: 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Conclusions: Protein expression changes suggest a central role of macrophage-driven immune dysregulation and complement activation in gastroparesis.

2019-09-15 | GSE130672 | GEO

RNA seq in human gastroparesis

Project description:Both diabetic and idiopathic gastroparesis have unique and overlapping changes in the transcriptome. Immune signaling predominately plays a role in the pathogenesis of gastroparesis.

2018-09-03 | GSE115601 | GEO

Proteomics in gastroparesis: unique and overlapping protein signatures in diabetic and idiopathic gastroparesis.

Project description: Not available

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miRNA sequencing profile of human plasma samples from healthy, diabetic, and gastroparesis patients

Project description:We report the high-throughput miRNA sequencing of plasma isolated from human patients with type 2 diabetes & gastroparesis, idiopathic gastroparesis alone, and healthy control patients.

2020-12-31 | GSE139577 | GEO

Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans

Project description:Idiopathic nodular mesangial sclerosis, also called idiopathic nodular glomerulosclerosis (ING) is a rare clinical entity with unclear pathogenesis. The hallmark of this disease is the presence of nodular mesangial sclerosis on histology without clinical evidence of diabetes mellitus or other predisposing diagnoses. To achieve insights into its pathogenesis, we queried the clinical, histopathologic and transcriptomic features of ING and nodular diabetic nephropathy (DN)

2020-12-09 | GSE162830 | GEO

Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis

Project description:Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from gastric tissue of 20 subjects (13 controls, 7 IG). Canonical markers, differential expression, and signalling were determined. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes (FDR<0.05). In IG, MM had decreased expression of tissue-protective and microglial genes and increased expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis to inflammatory sites were upregulated. In summary, human gastric muscle has a rich representation of immune cells; and IG patients demonstrate a higher expression of pro-inflammatory genes and signaling in MM. These data further link immune dysregulation to pathophysiology of gastroparesis.

2024-01-31 | GSE252126 | GEO

Proteomics of Vitreous Humor Reveals Upstream Regulators of Proliferative Diabetic Retinopathy

Project description:To investigate the key regulators of the disease by comparing the abundance of vitreous proteins between the patients with proliferative diabetic retinopathy (PDR) and the controls with idiopathic epiretinal membrane (iERM).

2021-07-26 | PXD027556 | iProX

Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans

Project description:Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans

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Common Immunologic Pathways Between Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis

Project description:The polyarticular and oligoarticular forms of juvenile idiopathic arthritis are classified as distinct entities. At the same time, many children who present with an oligoarticular phenotype eventually evolve to a polyarticular disease pattern, suggesting that the phenotypes might share with overlapping molecular mechanisms. Using gene expression microarrays, we found that 14 genes in neutrophils and 55 genes in PBMC shows common patterns of differential expression when children with active oligoarticular and polyarticular JIA were compared with healthy controls. These results demonstrate that there are commonalities between oligoarticular and polyarticular JIA that suggest overlapping immune mechanisms.

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Vitreous of proliferative diabetic retinopathy patients

Project description:We identified lncRNA expression profiles in vitreous samples between proliferative diabetic retinopathy (PDR) patients and idiopathic macular hole (IMH) patients, and between PDR patients who had received preoperative anti-vascular endothelial growth factor (anti-VEGF) therapy and PDR patients who had received surgery alone. There had been the systemic expression differences in vitreous at the microarray level from PDR patients and IMH patients, and from PDR patients after anti-VEGF treatment and untreated PDR patients.

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