Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1101692 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28897191_1.fastq.gz | Fastqsanger.gz | |||
| SRR28897191_2.fastq.gz | Fastqsanger.gz | |||
| SRR28897192_1.fastq.gz | Fastqsanger.gz | |||
| SRR28897192_2.fastq.gz | Fastqsanger.gz | |||
| SRR28897193_1.fastq.gz | Fastqsanger.gz |
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Project description:<p>Acute lung injury (ALI) is a lung disease characterized by an excessive inflammatory response and damage to lung epithelial cells. Atractylodin (ATL) is the main active component of Atractylodes lancea (Thunb.) DC., which has good anti-inflammatory activity and protects the integrity of the epithelial cell barrier. However, the efficacy of ATL in the treatment of ALI and its mechanism are unclear. We investigated the efficacy of ATL in treating ALI in vivo and in vitro, and explored its targets and mechanisms of action from metabolic and signaling pathways. The results showed that, in vivo, ATL significantly reduced the wet-dry ratio of lungs of rats with ALI, improved the pathological changes, reduced the aggregation and activation of neutrophils and macrophages in the lungs, and lowered the expression of the inflammatory factors, MCP-1, and MPO. The transcriptomics results suggested that ATL exerts its therapeutic effects by modulating the HIF-1 signaling pathway and metabolic processes. Metabolomics results showed that ATL mainly affected the processes of lactose degradation and galactose metabolism. Combined metabolomic and transcriptomic analyses showed that ASAH3L, a gene related to galactose metabolism, was regulated by ATL, and further experiments demonstrated that ATL reduced the expression of ASAH3L and ROS thereby inhibiting the activation of the HIF-1 signaling pathway. Overexpression of ASAH3L reversed the therapeutic effect of ATL in rats with ALI. In conclusion, ATL can reduce inflammation by inhibiting activating the HIF-1 signaling pathway and targeting ASAH3L to regulate galactose metabolism, thereby alleviating ALI.</p>
2024-07-23 | MTBLS9948 | MetaboLights
Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury.
2013-09-05 | GSE44925 | GEO
Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.
2013-09-05 | E-GEOD-44925 | biostudies-arrayexpress
Project description:Carbon metabolism in diverse bacteria is primarily governed by two key transcription factors, CRP and Cra. Although numerous studies have investigated their regulatory mechanisms under glucose conditions, the understanding of their role in controlling central metabolism across different carbon sources, such as galactose, remains limited, with scarce in vivo binding information available. In this study, we focused on the Cra binding profile of Escherichia coli grown on galactose, an unfavorable carbon source. While genome-wide Cra binding sites on galactose closely resemble that on glucose, however, further examination of transcriptomic and flux simulation data suggests a complex regulatory mechanism by which Cra modulates central carbon metabolism on galactose. Additionally, conservation analysis across a wide range of bacterial taxa revealed that Cra and its regulons are more broadly conserved compared to CRP and its regulons, indicating a potential role for Cra in the early evolution of bacterial central carbon metabolism.
2025-08-11 | GSE232784 | GEO
Project description:Carbon metabolism in diverse bacteria is primarily governed by two key transcription factors, CRP and Cra. Although numerous studies have investigated their regulatory mechanisms under glucose conditions, the understanding of their role in controlling central metabolism across different carbon sources, such as galactose, remains limited, with scarce in vivo binding information available. In this study, we focused on the Cra binding profile of Escherichia coli grown on galactose, an unfavorable carbon source. While genome-wide Cra binding sites on galactose closely resemble that on glucose, however, further examination of transcriptomic and flux simulation data suggests a complex regulatory mechanism by which Cra modulates central carbon metabolism on galactose. Additionally, conservation analysis across a wide range of bacterial taxa revealed that Cra and its regulons are more broadly conserved compared to CRP and its regulons, indicating a potential role for Cra in the early evolution of bacterial central carbon metabolism.
2025-08-11 | GSE119894 | GEO
Project description:The asparagine hydroxylase, factor inhibiting HIF (FIH) confers oxygen-dependence upon the hypoxia-inducible factor (HIF), a master regulator of the cellular adaptive response to hypoxia. Studies investigating whether asparagine hydroxylation is a general regulatory oxygen-dependent modification have identified multiple non-HIF targets for FIH. However the functional consequences of this outside of the HIF pathway remain unclear. Here, we demonstrate that the deubiquitinase ovarian tumor domain containing, ubiquitin aldehyde binding protein 1 (OTUB1) is a substrate for hydroxylation by endogenous FIH on N22. Mutation of N22 leads to a profound change in the interaction of OTUB1 with proteins important in cellular metabolism. Furthermore, mutant OTUB1 (lacking the hydroxylation site) impairs cellular metabolic processes when compared to wild type. Based on these data, we hypothesize that OTUB1 is a target for functional hydroxylation by FIH, and propose that this provides new insight into the regulation of cellular energy metabolism during hypoxia.
2017-03-28 | MSV000080695 | MassIVE
Project description:The addition of 2ME2 (HIF-1 inhibitor) to rat model of galactose-induced cataract decreased opacity and therapeutic effect. Genes regulated by 2ME2 addition were identified by microarray analysis. A total of 7 samples were analyzed: samples with no cataract (Control_Day4, Control_Day6), samples with cataract (Galactose-1, Galactose-2, Galactose-3), samples with decreased lens opacity (2ME2, 2ME2-2)
2024-02-16 | GSE240617 | GEO
Project description:In acute kidney injury (AKI) regions of the kidney are hypoxic. However, for reasons yet unknown, adaptation to hypoxia through hypoxia inducible factor (HIF) is limited. Here we seek for potential HIF repressors, their amenability to intervention, and assess the consequences for AKI outcome Renal miR-22 is up-regulated in AKI. In vitro, miR-22 is inducible by hypoxia, represses HIF, and this repression is offset by specific anti-miR-22 molecules. Inhibition of miR-22 in AKI leads to a complex regulation of more than 3,000 renal genes, most of which are unrelated to the HIF pathway.
2019-11-20 | GSE107710 | GEO
Project description:While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA-sequencing (scRNA-Seq), we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreERT2; Hif1afl/fl) significantly mitigated HO in vivo. ScRNA-Seq analysis of these Hoxa11-CreERT2; Hif1afl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion.
2024-03-15 | GSE255942 | GEO
Project description:Exposure to hypoxia requires adaptive mechanisms for survival. During acute hypoxia, Na,K-ATPase endocytosis in alveolar epithelial cells (AEC) occurs via protein kinase C zeta (PKCζ) phosphorylation of α1- Na,K-ATPase independently of the hypoxia inducible factor (HIF). However, exaggerated Na,K-ATPase down-regulation leads to cell death. Here we report that during prolonged hypoxia plasma membrane Na,K-ATPase levels were maintained at ~50% of normoxic values due to HIF mediated regulation of HOIL-1L which targets PKCζ for degradation. Silencing HOIL-1L in the lung epithelium prevented PKCζ degradation causing Na,K-ATPase downregulation. Accordingly, HIF regulation of HOIL-1L targets the phosphorylated PKCζ for degradation and serves as an hypoxia-adaptive mechanism to stabilize the Na,K-ATPase avoiding significant lung injury.
2018-02-14 | GSE102107 | GEO