N6-Methyladenosine Methylomic Landscape of Ureteral Deficiency in Reflux Uropathy and Obstructive Uropathy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE195849 | GEO | 2022/02/01
REPOSITORIES: GEO
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Project description:N6-Methyladenosine Methylomic Landscape of Ureteral Deficiency in Reflux Uropathy and Obstructive Uropathy
| PRJNA802275 | ENA
Project description:BackgroundCongenital anomalies of the kidneys and urinary tracts (CAKUT) represent the most prevalent cause for renal failure in children. The RNA epigenetic modification N 6-methyladenosine (m6A) methylation modulates gene expression and function post-transcriptionally, which has recently been revealed to be critical in organ development. However, it is uncertain whether m6A methylation plays a role in the pathogenesis of CAKUT. Thus, we aimed to explore the pattern of m6A methylation in CAKUT.MethodsUsing m6A-mRNA epitranscriptomic microarray, we investigated the m6A methylomic landscape in the ureter tissue of children with obstructive megaureter (M group) and primary vesicoureteral reflux (V group).ResultsA total of 228 mRNAs engaged in multiple function-relevant signaling pathways were substantially differential methylated between the "V" and "M" groups. Additionally, 215 RNA-binding proteins that recognize differentially methylated regions were predicted based on public databases. The M group showed significantly higher mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP) and significantly lower mRNA levels of m6A eraser (FTO) according to real-time PCR. To further investigate the differentially methylated genes, m6A methylome and transcriptome data were integrated to identified 298 hypermethylated mRNAs with differential expressions (265 upregulation and 33 downregulation) and 489 hypomethylated mRNAs with differential expressions (431 upregulation and 58 downregulation) in the M/V comparison.ConclusionThe current results highlight the pathogenesis of m6A methylation in obstructive and reflux uropathy.
| S-EPMC9251069 | biostudies-literature
Project description:Transcriptional profiling of adult esophageal epithelium comparing wild-type mice with Nrf2-/- mice with or without gastroesophageal reflux for 4 weeks. Goal was to determine the role of Nrf2 on the barrier function of mouse esophageal epithelium. Two-class comparisons. Wild-type/without reflux vs. Nrf2-/-/without reflux; Wild-type/gastric reflux vs. Nrf2-/-/gastric reflux; Wild-type/duodenal reflux vs. Nrf2-/-/duodenal reflux; Wild-type/mixed reflux vs. Nrf2-/-/mixed reflux. Biological replicates: 3 replicates for each group.
2013-01-01 | E-GEOD-39629 | biostudies-arrayexpress
Project description:Vesicoureteral reflux (VUR) is a common pediatric condition that predisposes children to renal damage after urinary tract infection (UTI). We profiled the urinary proteome of VUR patients with recurrent UTI and renal scarring to identify potential biomarkers characterizing this condition. Urine was obtained from 22 age-matched controls and 22 patients with low grade VUR (1-3 out of 5), renal scarring, and history of recurrent UTI. Proteins extracted from these samples were analyzed by mass spectrometry for protein identification and quantitation for comparison.
2018-10-05 | PXD010469 | Pride
Project description:Non-Erosive Reflux Disease (NERD) is one of the most prominent and common forms of gastroesophageal reflux disease (GERD). We performed transcriptomic analysis (RNA sequencing) of esophageal biopsies from patients with NERD and healthy controls to increase understanding of complex cellular and molecular pathways in NERD.
2021-12-01 | GSE182974 | GEO
Project description:The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammatory-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett’s esophagus and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague Dawley rats, with or without reflux-induction received water or C-PAC ad libitum (700 µg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis, and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory and immune-implicated proteins and genes including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1β, Lbp, Lcn2, Myd88, Nfkb1, Tlr2 and Tlr4 aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation and cellular damage.
2024-02-08 | GSE254633 | GEO
Project description:Identification of Novel Immune Cell Signature in Gastroesophageal Reflux Disease: Altered Mucosal Mast Cells and Dendritic Cell Profile. The mechanisms underlying the most troublesome symptom of gastroesophageal reflux disease (GERD), heartburn, remain incompletely understood. The pathogenesis of heartburn in GERD is likely to involve not only central mechanisms of sensitization including hypervigilance, but also multiple mucosal factors including maintenance of epithelial barrier integrity via tight junction proteins, expression of acid-sensing ion channels on nerve endings, and mucosal inflammation . We hypothesized that immune cell components play a regulatory role in mucosal mechanisms of sensitization in GERD, and aimed to identify differences in the immune cell signature and sensory mucosal markers between reflux phenotypes and healthy asymptomatic subjects.
2023-11-20 | GSE226303 | GEO
Project description:There is no useful biomarker for reflux esophagitis. The aim of this study is to establish novel diagnosis marker for RE by using miRNA.
2017-03-15 | GSE94719 | GEO
Project description:Background & Aims: Because the pathophysiology of GERD is not fully understood, presently used drug target only one or more of the known underlying mechanisms but are not fully effective in all patients. 1Identifying novel central targets may pave the way to develop more effective agents. Methods: A surgical model of sub-chronic reflux esophagitis was developed. Wistar rats were pretreated for 7days with omeprazole (standard proton pump inhibitor) or STW5 (herbal preparation of established efficacy in gastro-intestinal disorders). Treatment was continued for 10days after surgery, rats were sacrificed and esophagi excised. Histological, proteomic and transcriptomic methods were applied to identify reflux induced changes and treatment responses. Results: Protection against reflux induced inflammation was achieved by both test drugs. Both reduced macroscopic and microscopic lesions of the esophagi as well as most measured pro-inflammatory cytokines without significantly affecting NF-kB activity. Proteomic and transcriptomic analysis identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as highly relevant mediators in GERD. Other highly regulated genes were those of IL-6, CCL3, CCL7 and LOX-1. Many affected cyto-/chemokines were involved in the TREM-1 signaling pathway. The fatty acid receptor GPR84 was highly up-regulated in esophagitis but down-regulated by both drugs. This was confirmed by Western blot and immune-histochemical staining, showing for the first time expression of this receptor in esophageal tissue and its possible involvement in GERD. Conclusion: STW5 and omeprazole target a broad spectrum of molecules involved in immunological and inflammatory processes, of which IL-8 (CINC1-3), TREM-1 pathway and GPR84 are proposed to be most promising novel targets for the treatment of GERD. Refluxesophagitis was surgically induced. Wistar rats were pretreated for 7 days with omeprazole or STW5. Treatment was continued for 10days after surgery, rats were sacrificed and esophagi exiced. The study had 5 groups. Group 1: sham operated, Group 2: esophagitis group, untreated, Group3: esophagitis treated with STW5 0.5ml/kg. Group 4: esophagitis treated with STW5 2ml/kg. Group 5: esophagitis treated with Omeprazole (30mg/kg). 4 microarrays from esophageal tissue and blood from 4 animals of each group were performed.
2015-12-16 | E-GEOD-63401 | biostudies-arrayexpress
Project description:Background & Aims: Because the pathophysiology of GERD is not fully understood, presently used drug target only one or more of the known underlying mechanisms but are not fully effective in all patients. 1Identifying novel central targets may pave the way to develop more effective agents. Methods: A surgical model of sub-chronic reflux esophagitis was developed. Wistar rats were pretreated for 7days with omeprazole (standard proton pump inhibitor) or STW5 (herbal preparation of established efficacy in gastro-intestinal disorders). Treatment was continued for 10days after surgery, rats were sacrificed and esophagi excised. Histological, proteomic and transcriptomic methods were applied to identify reflux induced changes and treatment responses. Results: Protection against reflux induced inflammation was achieved by both test drugs. Both reduced macroscopic and microscopic lesions of the esophagi as well as most measured pro-inflammatory cytokines without significantly affecting NF-kB activity. Proteomic and transcriptomic analysis identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as highly relevant mediators in GERD. Other highly regulated genes were those of IL-6, CCL3, CCL7 and LOX-1. Many affected cyto-/chemokines were involved in the TREM-1 signaling pathway. The fatty acid receptor GPR84 was highly up-regulated in esophagitis but down-regulated by both drugs. This was confirmed by Western blot and immune-histochemical staining, showing for the first time expression of this receptor in esophageal tissue and its possible involvement in GERD. Conclusion: STW5 and omeprazole target a broad spectrum of molecules involved in immunological and inflammatory processes, of which IL-8 (CINC1-3), TREM-1 pathway and GPR84 are proposed to be most promising novel targets for the treatment of GERD. Refluxesophagitis was surgically induced. Wistar rats were pretreated for 7 days with omeprazole or STW5. Treatment was continued for 10days after surgery, rats were sacrificed and esophagi exiced. The study had 5 groups. Group 1: sham operated, Group 2: esophagitis group, untreated, Group3: esophagitis treated with STW5 0.5ml/kg. Group 4: esophagitis treated with STW5 2ml/kg. Group 5: esophagitis treated with Omeprazole (30mg/kg). 4 microarrays from esophageal tissue and blood from 4 animals of each group were performed.
2015-12-16 | E-GEOD-63402 | biostudies-arrayexpress