Estrogen-related receptor γ agonist DY131 ameliorates lipopolysaccharide-induced acute liver injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE160880 | GEO | 2020/11/06
REPOSITORIES: GEO
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Project description:Estrogen-related receptor γ agonist DY131 ameliorates lipopolysaccharide-induced acute liver injury
| PRJNA674766 | ENA
Project description:Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs characterized by increased permeability of the alveolar-capillary membrane with subsequent interstitial/alveolar edema and diffuse alveolar damage. ALI/ARDS can be the results of either direct or indirect lung injury, with pneumonia being the most common direct pulmonary insult and sepsis the most common extra-pulmonary cause. In this study, we employed the murine lipopolysaccharide (LPS)-induced direct and indirect lung injury model to explore the pathogenic mechanisms of pulmonary and extra-pulmonary ARDS, using an unbiased, discovery and quantitative proteomic approach. A total of 1,017 proteins were both identified and quantified in bronchoalveolar lavage fluid (BALF) from control, intratracheal LPS (I.T. LPS, 0.1 mg/kg) and intraperitoneal LPS (I.P. LPS, 5 mg/kg) treated mice. The two LPS groups shared 13 up-regulated and 22 down-regulated proteins compared to the control group. Among them, molecules related to bronchial and type II alveolar epithelial cell functions including cell adhesion molecule 1 and surfactant protein B were reduced, whereas lactotransferrin and resistin like alpha involved in lung innate immunity were upregulated in both LPS groups. Proteomic profiling also identified significant differences in BALF proteins between I.T. and I.P. LPS groups. Ingenuity pathway analysis revealed that acute-phase response signaling was activated by both I.T. and I.P. LPS, however, the magnitude of activation is much greater in I.T. LPS group compared to I.P. LPS group. Intriguingly, two canonical signaling pathways, liver X receptor/retinoid X receptor activation and the production of nitric oxide and reactive oxygen species in macrophages, were activated by I.T. LPS but suppressed by I.P. LPS. In addition, CXCL15 (also known as lungkine) was also up-regulated by I.T LPS but down-regulated by I.P. LPS. In conclusion, our quantitative discovery-based proteomic approach identified commonalities as well as significant differences in BALF protein expression profiles in LPS-induced direct and indirect lung injury, and importantly, LPS-induced indirect lung injury results in suppression of select components of lung innate immunity, which could contribute to the so-called “immunoparalysis” in sepsis patients.
2019-07-11 | PXD014070 | Pride
Project description:The study investigated the acute and simultaneous response of the mammary and liver transcriptome to an intra-mammary lipopolysaccharide (LPS) challenge in early-lactating cows, and its consequences on metabolic biomarkers and liver composition. At 7 days of lactation, 7 cows served as controls (CTR) and 7 cows (LPS) received an intra-mammary E. coli LPS challenge. The mammary and liver tissues were sampled at 2.5 h from challenge for transcriptomic profiling. Liver composition was evaluated at 2.5 h and 7 d after challenge and blood biomarkers were analized at -2, 3, 7 and 14 d from challenge. In mammary tissue, the LPS challenge resulted in 189 differentially expressed gene (DEG), with 20 downregulated and 169 upregulated, while in the liver were found 107 DEG with 42 downregulated and 65 upregulated in LPS vs CTR. In the udder, the Dynamic Impact Approach (DIA) highlighted the activation of NOD-like receptor signaling, Toll-like receptor signaling, RIG-I-like receptor signaling and Apoptosis pathways, while in the liver were inhibited the Fatty acid elongation in mitochondria and activated the p53 signaling pathway. The LPS induced the alteration of liver lipid metabolism (rise of total lipid and triglyceride concentration), a systemic inflammation (rise of blood ceruloplasmin and bilirubin) and an increase of body fat mobilization. In cows subjected to intra-mammary LPS, the mammary gland responds activating mechanisms of pathogen recognition. In the liver the response likely depends by mediators coming from udder and affects the liver functionality and mainly the fatty acid metabolism.
2014-12-17 | GSE64225 | GEO
Project description:The subject of the current study is the finding of possible molecular partners of drosophila EcR receptor. The whole-genome experiments revealed that the sites of EcR receptor are partially overlapped with ERR binding sites. As ERR receptor specifically binds regulatory regions of glycolytic genes and genes of glycogen metabolism, the presence of EcR on ERR targets signifies involvement of the ecdysone signaling in regulation of carbohydrate metabolism.
2019-07-16 | GSE122810 | GEO
Project description:To investigate the role of recipient neutrophil intracellular HMGB1 in early allograft injury after liver transplant. Using a mouse orthotopic liver transplant model, as well as LPS injection, we found that neutrophils significantly infiltrate the liver after liver transplant and LPS challenge. Deficiency of neutrophil HMGB1 enhances their activation, boosts their pro-oxidant and pro-inflammatory phenotype, and hinders biosynthesis and metabolism of inositol polyphosphates. Overall, these events exacerbate early allograft injury after liver transplant.
2023-07-27 | GSE225106 | GEO
Project description:Lactoferrin (LF) is an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and neutrophils in mammals. In this study, we created a mouse model of lipopolysaccharide (LPS)-induced acute lung injury and explored the anti-inflammatory effect and mechanism of bovine lactoferrin (bLF) in acute lung injury using the RNA sequencing (RNA-seq) technology and transcriptome analysis.
2023-12-19 | GSE247266 | GEO
Project description:The study investigated the acute and simultaneous response of the mammary and liver transcriptome to an intra-mammary lipopolysaccharide (LPS) challenge in early-lactating cows, and its consequences on metabolic biomarkers and liver composition. At 7 days of lactation, 7 cows served as controls (CTR) and 7 cows (LPS) received an intra-mammary E. coli LPS challenge. The mammary and liver tissues were sampled at 2.5 h from challenge for transcriptomic profiling. Liver composition was evaluated at 2.5 h and 7 d after challenge and blood biomarkers were analized at -2, 3, 7 and 14 d from challenge. In mammary tissue, the LPS challenge resulted in 189 differentially expressed gene (DEG), with 20 downregulated and 169 upregulated, while in the liver were found 107 DEG with 42 downregulated and 65 upregulated in LPS vs CTR. In the udder, the Dynamic Impact Approach (DIA) highlighted the activation of NOD-like receptor signaling, Toll-like receptor signaling, RIG-I-like receptor signaling and Apoptosis pathways, while in the liver were inhibited the Fatty acid elongation in mitochondria and activated the p53 signaling pathway. The LPS induced the alteration of liver lipid metabolism (rise of total lipid and triglyceride concentration), a systemic inflammation (rise of blood ceruloplasmin and bilirubin) and an increase of body fat mobilization. In cows subjected to intra-mammary LPS, the mammary gland responds activating mechanisms of pathogen recognition. In the liver the response likely depends by mediators coming from udder and affects the liver functionality and mainly the fatty acid metabolism. Fourteen Holstein cows entering their second or greater lactation were used. Cows were housed in a ventilated tie-stall barn and were fed a common lactation diet (Net energy of lactation = 1.69 Mcal/kg DM) as a total mixed ration once daily (0600 h) and milked twice daily (0400 and 1600 h). A bovine oligonucleotide (70-mers) microarray with >13,000 annotated sequences developed at the University of Illinois, was used for transcript profiling. Details on the development, annotation, and use of this microarray have been reported previously by Loor et al., 2007 (http://physiolgenomics.physiology.org/content/32/1/105.abstract). Methods for microarray hybridization and scanning were as reported by Loor et al. (2007). Briefly, slides were hydrated, dried, and placed in a UV Stratalinker 1800 (Stratagene, La Joya, CA) for ~5 min. Slides were washed with 0.2% SDS solution, rinsed with MilliQ (Millipore) H2O, and placed in warm prehybridization soln for 45 min at 42 C. The same amount of Cy3- or Cy5-labelled cDNA from mammary or liver and a reference standard RNA pool (made of different bovine tissues) were co-hybridized using a dye-swap design (i.e., two microarrays per sample). Slides were incubated for 48 h at 45 C prior to scanning. Criteria for evaluation of slide quality included: identification of number of spots with a minimum median signal intensity of 3 SD above background; keeping slides with a minimum of 20,000 spots with minimum median signal intensity of 3 SD above background in both Cy3 and Cy5 channels; and keeping slides with a minimum mean intensity of 400 relative fluorescent units in both Cy3 and Cy5 channels across the entire slide. Data from a total of 112 microarrays were normalized for dye and microarray effects (i.e., Lowess normalization and microarray centering) and used for statistical analysis. Data were analyzed using the Proc MIXED procedure of SAS (SAS, SAS Inst. Inc., Cary, NC). Fixed effects were treatment (LPS challenge, control (no infsuion)) and dye. Random effects included cow and microarray. Raw P values were adjusted using Benjamini and HochbergM-bM-^@M-^Ys false discovery rate (FDR). Differences in relative expression due to treatment were considered significant at an FDR-adjusted P < 0.05. For a more stringent characterization between the two treatments, a 1.5-fold difference in mRNA expression was set as threshold among differentially expressed genes.
2014-12-17 | E-GEOD-64225 | biostudies-arrayexpress
Project description:Cholestasis is characterized by hepatic accumulation of cytotoxic bile acids (BAs), which often subsequentlyleads to liver injury, inflammation, fibrosis, and ultimately liver cirrhosis. Fibroblast growth factor 21 (FGF21) is a liver secreted hormone with pleiotropic effects on the homeostasis of glucose, lipid, and energy metabolism. However, whether hepatic FGF21 plays a role in cholestatic liver injury remains elusive. We found that serum and hepatic FGF21 levels were significantly increased in response to cholestatic liver injury. Hepatocyte-specific deletion of Fgf21 exacerbated hepatic accumulation of BAs, further accentuating liver injury. Consistently, administration of rFGF21 ameliorated cholestatic liver injury in α-naphthylisothiocyanate (ANIT)-treated and Mdr2 deficiency mice. Mechanically, FGF21 activated a hepatic FGFR4-JNK signaling pathway to decrease Cyp7a1 expression, thereby reducing hepatic BAs pool. Our study demonstrates that hepatic FGF21 functions as an adaptive stress-responsive signal to downregulate BA biosynthesis, thereby ameliorating cholestatic liver injury, and FGF21 analogs may represent a candidate therapy for cholestatic liver diseases.
2023-08-19 | GSE240733 | GEO
Project description:Purpose: The goal of this study is to compare transcriptome profilings of liver from GBP5 knockout and WT control mice treated with GalN/LPS. Methods: GBP5 knockout and WT control mice were treated with GalN (800 μg/g body weight) and LPS (100 ng/g body weight) for 6 h to induce liver inflammation and injury. RNA samples were pooled from livers of GBP5 KO and WT mice (n=4 for each group). RNA-seq was performed by using HiSeq X Ten platform. Paired-end clean reads were aligned to the mouse reference genome (Ensembl_GRCm38.89) with TopHat (version 2.0.12), and the aligned reads were used to quantify mRNA expression by using HTSeq-count (version 0.6.1). Conclusion: Our study represents the first detailed analysis of liver transcriptomes from GBP5 KO and WT mice treated with GalN/LPS, generated by RNA-seq technology. The RNA-seq analysis showed that 405 genes were down-regulated and 33 genes were up-regulated in the liver of GBP5 KO mice. GO analysis showed that the down-regulated genes were primarily related to the immune system process and response to stress. KEGG pathway enrichment analysis showed that phagocytosis and Jak-STAT signaling pathway were significantly decreased in the liver of GBP5 KO mice.
2021-12-28 | GSE124473 | GEO
Project description:To further elucidate the role of miRNAs, HTS was used to screen differential miRNAs. Mice hippocampus from the saline group, the LPS group, and the LPS+GAS group were removed to analyze using HTS.
2022-10-09 | GSE214909 | GEO