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Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [PCI34051 study]

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE213191 | GEO | 2022/09/16

REPOSITORIES: GEO

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Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis.

Project description:Epigenetic alterations are especially important in necrotizing enterocolitis (NEC). Here, we reported that histone deacetylase 8 (HDAC8) plays a previously unknown role in modulating arginine metabolism via acetylation of histone 3 lysine 9 (acetyl-H3K9) regulation during the pathogenesis of NEC. We found that HDAC8 was upregulated in humans and mice intestinal samples with NEC, while selective inhibition of HDAC8 expression ameliorated NEC. HDAC8 regulates enzymes involved in the metabolic conversion of proline to arginine (PRODH, PRODH2, OAT, and OTC) and arginine to ornithine (ARG1). The results showed that H3K9ac signal in the PRODH/PRODH2 promoter region was mediated by HDAC8. Additionally, the decreased concentration of butyric acid was strongly correlated with elevated HDAC8 levels and circulating arginine, which may result from an unbalanced Firmicutes/Bacteroidetes ratio. These results reveal previously underappreciated roles of microbial metabolites and HDAC8 to coordinate the arginine metabolism during NEC development.

| S-EPMC10227426 | biostudies-literature

Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis

Project description:To further explore the role of HDAC8 in NEC, we analyzed the signaling pathways that were altered in mice with NEC. We then performed gene expression profiling analysis using data obtained from RNA-seq of intestinal tissues (control group, NEC group).

2023-05-04 | GSE212694 | GEO

Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [CUT&Tag]

Project description:To verify that arginine metabolic enzymes are directly regulated by H3K9ac, we established FHs74Int cells and HDAC8-overexpressing FHs74Int cells We then performed gene expression profiling analysis using data obtained from CUT&Tag of 4 different treatment conditions in control or HDAC8 stably overexpressed FHs74Int cells ,which treated with PCI34051 (10 µmol/L for 24 h) or LPS (10 µg/ml for 48 h).

2022-09-16 | GSE213190 | GEO

Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [RNA-seq]

Project description:To determine which signaling pathway may have been affected by HDAC8, we designed NEC mice model with PCI34051 supplementation. We then performed gene expression profiling analysis using data obtained from RNA-seq of intestinal tissues (control group, NEC group, PCI34051+NEC group) treated with PCI34051 (10 mg/kg/d).

2022-09-16 | GSE213187 | GEO

Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis

Project description:Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis

| PRJNA876828 | ENA

Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [PCI34051 study]

Project description:Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [PCI34051 study]

| PRJNA879722 | ENA

Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [RNA-seq]

Project description:Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [RNA-seq]

| PRJNA879694 | ENA

Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [CUT&Tag]

Project description:Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [CUT&Tag]

| PRJNA879731 | ENA

Surgical necrotizing enterocolitis.

Project description:Although currently available data are variable, it appears that the incidence of surgical necrotizing enterocolitis (NEC) has not decreased significantly over the past decade. Pneumoperitoneum and clinical deterioration despite maximal medical therapy remain the most common indications for operative treatment. Robust studies linking outcomes with specific indications for operation are lacking. Promising biomarkers for severe NEC include fecal calprotectin and S100A12; serum fatty acid-binding protein; and urine biomarkers. Recent advances in ultrasonography make this imaging modality more useful in identifying surgical NEC and near-infrared spectroscopy (NIRS) is being actively studied. Another fairly recent finding is that regionalization of care for infants with NEC likely improves outcomes. The neurodevelopmental outcomes after surgical treatment are known to be poor. A randomized trial near completion will provide robust data regarding neurodevelopmental outcomes after laparotomy versus drainage as the initial operative treatment for severe NEC.

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Probiotics and necrotizing enterocolitis.

Project description:In this review, we summarize existing knowledge regarding the effects of probiotics on necrotizing enterocolitis (NEC). We review the role of the microbiome in NEC and pre-clinical data on mechanisms of probiotic action. Next, we summarize existing randomized controlled trials and observational studies of probiotics to prevent NEC. We also summarize findings from several recent meta-analyses and report a new cumulative meta-analysis of probiotic trials. Finally, we review data from cohorts routinely using commercially available probiotics. Our goal is to inform clinicians about the risks and benefits of probiotics, which may be helpful for those considering use in preterm infants to prevent NEC, death, or sepsis.

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