MRNA Expression data from rats treated with ANIT or vehicle
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE72387 | GEO | 2015/08/26
SECONDARY ACCESSION(S): PRJNA293936
REPOSITORIES: GEO
Similar Datasets
Project description:Adult Sprague Dawley rats were treated i.g. with 50 mg/kg alpha-naphthylisothiocyanate (ANIT) or vehicle (corn oil). Hepatobiliary liver injury occurred at 24 h postdose in ANIT rats with repair at 120h. Livers were extracted from rats at 24h and 120 h post ANIT exposure. This study investigated differences in mRNA expression between the injury and repair phases in the context of ANIT exposure. 8 week male Sprague Dawley rats were administered ANIT or vehicle for quantification of hepatobiliary injury via clinical chemistry biomarkers and pathology between 6 and 168 h postdosing. Rats sacrificed at 24 h and 120h postdosing coincided with peak injury and injury resolution, respectively.
2015-08-26 | E-GEOD-72387 | biostudies-arrayexpress
Project description:Purpose: The goals of this study was to (1) evaluate the protective effect of celastrol on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis and (2) which genes were recovered by celastrol. Methods:To investigate the protective effect of celastrol on ANIT-induced cholestasis, the WT mice were randomly assigned into two groups, respectively (n=3): (1) ANIT; (2) ANIT+Celastrol. ANIT+Celastrol group was orally treated with celastrol (10 mg/kg dissolved in 1% DMSO + 2% Tween 80 + 97% water) for 5 consecutive days. After celastrol was treated for 3 days, ANIT and ANIT+Celastrol groups were given a single oral dose of ANIT. All mice were killed 48 h after ANIT administration. Liver samples were harvested and frozen at -80 °C before analysis. Results: A total of 978 DEGs were identified. Large numbers of these DEGs were related to activation of SIRT1, which included increased FXR signaling and inhibition of PPARγ, nuclear factor-kappa B (NF-κB), and P53 signaling. Conclusions: Celastrol could protect ANIT-induced cholestasis by recovering disrupted Sirt1 level.
2018-02-09 | GSE110391 | GEO
Project description:Acute toxic responses to a single 50 mg/kg oral dose of 1-napthylisothiocyanate (ANIT) were evaluated by microarray analysis of laser capture-microdissected rat biliary epithelium or hepatic parenchyma at 2 and 6 hours post-dose. Selective and dramatic differences between the biliary epithelium and the hepatic parenchyma were evident as soon as 2 hours at which time 375 genes were altered in biliary epithelium, but only a nominal 38 genes were altered in the hepatic parenchyma. Gene expression analysis revealed increased expression of genes involved in the unfolded protein response and ER stress in biliary epithelial cells, but no alteration of these genes in hepatocytes. By 6 hours post dose, 620 genes showed altered expression in biliary epithelium while there were only 32 genes altered in hepatic parenchyma. At this timepoint, analysis of the biliary epithelium revealed decreased expression of genes involved in the unfolded protein response compared to the 2 hour time point, and increased expression at 6 hours of genes involved in protein degradation such as proteasome-ubquination pathways, and genes associated with cell death. Our analysis revealed early loss of biliary epithelial integrity and attempts at repair of damage with subsequent activation of protein degradation and cell fate decisions leading to death pathways within a 6 hour time course. During this same time interval, hepatic parenchymal gene expression changed little and mainly reflected a decrease in enterohepatic circulation of bile acids and an increase in ribosomal proteins which may signal an adaptive change to reduced bile acid delivery to the liver and an increased demand for bile acids and glutathione-mediated transport of ANIT. This versatile approach provides a precise evaluation of distinct cell populations, biliary epithelium and hepatic parenchyma, in situ. (Cullen et.al., Toxicologic Pathology 2010) Rat were exposed to a single dose of 1-napthylisothiocyanate (ANIT) or vehicle. Laser capture-microdissection was used to isolate rat biliary epithelium or hepatic parenchyma at 2 and 6 hours post-dose. Affymetrix GeneChips and Rosetta Resolver were used to determine differential gene expression.
2010-03-09 | E-GEOD-20498 | biostudies-arrayexpress
Project description:The aim of the present study was to investigate the therapeutic mechanism of the anti-cholestatic effects of melatonin against ANIT-induced liver injury in rats, and to screen for potential biomarkers of cholestasis through isobaric tags for relative and absolute quantitation (iTRAQ) quantitative proteomics.
2020-12-16 | PXD023155 | iProX
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:Acute toxic responses to a single 50 mg/kg oral dose of 1-napthylisothiocyanate (ANIT) were evaluated by microarray analysis of laser capture-microdissected rat biliary epithelium or hepatic parenchyma at 2 and 6 hours post-dose. Selective and dramatic differences between the biliary epithelium and the hepatic parenchyma were evident as soon as 2 hours at which time 375 genes were altered in biliary epithelium, but only a nominal 38 genes were altered in the hepatic parenchyma. Gene expression analysis revealed increased expression of genes involved in the unfolded protein response and ER stress in biliary epithelial cells, but no alteration of these genes in hepatocytes. By 6 hours post dose, 620 genes showed altered expression in biliary epithelium while there were only 32 genes altered in hepatic parenchyma. At this timepoint, analysis of the biliary epithelium revealed decreased expression of genes involved in the unfolded protein response compared to the 2 hour time point, and increased expression at 6 hours of genes involved in protein degradation such as proteasome-ubquination pathways, and genes associated with cell death. Our analysis revealed early loss of biliary epithelial integrity and attempts at repair of damage with subsequent activation of protein degradation and cell fate decisions leading to death pathways within a 6 hour time course. During this same time interval, hepatic parenchymal gene expression changed little and mainly reflected a decrease in enterohepatic circulation of bile acids and an increase in ribosomal proteins which may signal an adaptive change to reduced bile acid delivery to the liver and an increased demand for bile acids and glutathione-mediated transport of ANIT. This versatile approach provides a precise evaluation of distinct cell populations, biliary epithelium and hepatic parenchyma, in situ. (Cullen et.al., Toxicologic Pathology 2010)
2010-02-24 | GSE20498 | GEO
Project description:The protective effect of celastrol in ANIT-induced cholestasis
| PRJNA433590 | ENA
Project description:Intrahepatic cholestasis (IC) is a common symptom of liver diseases but with limited treatment. Huangqi decoction (HQD), a classic herbal medicine, has shown protective effects against IC. In this study, the iTRAQ-based quantitative proteomics was performed to investigate the potential mechanism of HQD on alpha-naphthylisothiocyanate (ANIT) induced IC, resulting in 2,796 quantified proteins across all the samples, including 270 differentially expressed proteins under HQD treatment. Fuzzy c-means (FCM) clustering analysis of these 270 proteins revealed that the pro-inflammatory proteins, such as LCN2, SAA1, FGG, FGA, and FGB, were assigned in the Cluster 1 (up-regulated by ANIT, and down-regulated by HQD). Following functional bioinformatics analysis and protein-protein interaction (PPI) network analysis represented that these pro-inflammatory proteins were involved in the STAT3 signaling pathway. Further real-time PCR and Western blot experiments confirmed that the expression of these proteins was consistent with the proteomic results. Moreover, HQD treatment decreased the phosphorylation of STAT3 that induced by ANIT. And Western blot experiments also revealed that HQD could decrease phosphorylation of NF-κB and down-regulate the expression inflammatory genes IL-6, and therefore inhibit IL-6/STATA3 signaling pathway. In summary, the present study suggested that HQD treatment may ameliorate intrahepatic cholestasis via inhibiting the NF-κB/IL-6/STAT3 signaling pathway.
2020-01-13 | PXD014882 | Pride
Project description:Periurethral human mesenchymal stem cell (hMSC) injections are associated with functional improvement in animal models of post-partum stress urinary incontinence (SUI). However, limited data exists on the role of hMSCs in modulating gene expression in tissue repair after urethral injury. We quantified temporal gene expression modulation in hMSCs, and injured rat urethral tissue, using RNA seq in an animal model of SUI, over a 3-day time period following urethral injury, and local hMSC therapy. We injected PKH fluorescent-labeled human hMSC into the periurethral space of rats, following a 4h vaginal distention (3 rats per time point). Control rats underwent vaginal distention injury only, and were sacrificed at 12h, 24h, 36h, 72h post injury. Rat urethral and vaginal tissues were frozen and sectioned. Fluorescent labeled hMSCs were distinguished from adjacent, unlabeled rat urethral tissue. RNA was prepared from urethral tissue obtained by laser dissection of frozen tissue sections and sequenced on an Illumina HiSeq 2500. Differentially expressed genes (DEGs) over 72h were evaluated using a 2-group t-test (p<0.05). Our transcriptional analyses identified candidate genes involved in tissue injury, that were broadly sorted by injury and exposure to hMSC, throughout the first 72h of acute phase of injury. DEGs in treated urethra, compared with untreated urethra, were functionally associated with tissue repair, angiogenesis, neurogenesis, and oxidative stress suppression. DEGs included a variety of cytokines, extracellular matrix stabilization and regeneration genes, cytokine signaling modification, cell cycle regulation, muscle differentiation and stabilization. Moreover, our results revealed DEGs changes in the hMSCs (PKH-labelled), which were harvested from injured urethra. The expressions are related to DNA damage repair, transcription activation, stem cell regulation, cell survival, apoptosis, self-renewal, cell proliferation, migration and injury response.
2020-06-30 | GSE149072 | GEO
Project description:Male Sprague Dawley rats were treated orally for 5 days with reference hepatotoxicants, each at a single dose level, alpha-naphthylisothiocyanate 100mg/kg (vehicle 5ml/kg corn oil); carbon tetrachloride 1582mg/kg (vehicle 5ml/kg corn oil); methylenedianiline 100mg/kg (vehicle 35% ethanol); acetaminophen 1000mg/kg (vehicle 2ml/kg corn oil); diclofenac 10mg/kg (vehicle 10ml/kg water)
2018-11-20 | GSE122315 | GEO