RNA-Seq Transcriptomic analysis in tumor and non-tumor tissues of Atg7-/- and Atg7-/-/Hmgb1-/- livers
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139153 | GEO | 2022/10/18
REPOSITORIES: GEO
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Project description:Ischemia/reperfusion injury (IRI) occurs in liver transplantations and major resections and can lead to liver dysfunction. HMGB1 locates in nucleus of normal hepatocytes, but translocates to cytoplasm and the extracellular space during IRI. Although the functions of nuclear and extracellular HMGB1 are well explored, the role cytoplasmic HMGB1 plays in hepatic IRI is still unknown. We hypothesize cytoplasmic HMGB1 interacts with binding proteins involved in the hepatocellular response to IRI. In this study binding proteins of cytoplasmic HMGB1 during hepatic IRI were identified. Normal and warm ischemia reperfusion (WI/R) liver tissues were used for cytoplasmic protein extraction. The protein extracts were subjected to co-immunoprecipitation to enrich HMGB1-protein complexes. To identify the immunoprecipitated proteins in eluates, 2DE and subsequent MS detection were performed. Three identified proteins were verified using western blotting: betaine--homocysteine S-methyltransferase 1 (BHMT), cystathionine gamma-lyase (CTH) and ATP synthase beta subunit (ATP5B). All three identified proteins have a role in metabolic pathways and autophagy. Our results demonstrate cytoplasmic HMGB1 binds to BHMT, CTH and ATP5B during hepatic WI/R. Since both, cytoplasmic HMGB1 and binding proteins, are involved in autophagy, we speculate this protein complex may be involved in the hepatocellular response to IRI via the autophagy pathway.
2017-03-10 | PXD003538 | Pride
Project description:Autophagy deficiency caused by conditional knockout of Atg7 results in severe hepatitis accompanied by abundant accumulation of p62. p62 stablizes Nrf2 by disrupting the association between Keap1 and Nrf2. To understand the pathogenesis of hepatitis under the autophagy deficiency, we examined gene expression profiles of livers from Atg7-null, Nrf2-null and Atg7-Nrf2 double mutant mice. Eight week old Atg7F/F:Mx1-Cre mice and Atg7F/F:Mx1-Cre:Nrf2-/- together with control mice were injected with pIpC. At 4 weeks after pIpC injection, total RNAs were purified from each mouse liver.
2010-10-14 | E-GEOD-20415 | biostudies-arrayexpress
Project description:The gene expression of normal and tumor tissues isolated from WT mice were compared with tumor tissues isolated from mice harboring liver specific deletion of HMGB1
2018-06-06 | GSE89689 | GEO
Project description:Dysregulation and abnormal expression of inflammatory mediators by keratinocytes promote the pathogenesis of the skin inflammation such as allergic contact dermatitis (ACD). High-mobility group box 1 (HMGB1) protein, a prototypical damage-associated molecular pattern (DAMP), that is expressed in the nucleus but released extracellularly upon inflammation has gained attention as an accelerator for skin inflammation. However, in vivo role of HMGB1 in ACD and other skin disorders remains to be elusive. In this study, we generated conditional knockout mice in which HMGB1 is deleted in keratinocytes and examined its role in skin inflammation models including 2,4-dinitrofluorobenezene (DNFB)-induced ACD. Unexpectedly, deletion of HMGB1 in keratinocytes exacerbated skin inflammation, accompanied by increased ear thickening. Elevated mRNA expression of interleukin-24 (IL-24), a known cytokine which promotes the pathogenesis of ACD, was also observed in the skin lesion of the mice. In accordance with above observations, both constitutive and IL-4-induced Il24 mRNA expression in vitro was augmented in hmgb1-deficient primary mouse keratinocytes and keratinocyte cell line PAM212 cells. Chromatin immunoprecipitation (ChIP) analysis revealed increased binding of tri-methyl histone H3 (lys4) (H3K4me3), a well-known histone mark for transcription active genes, to the promoter region of the Il24 gene in the hmgb1-deficient cells. ChIP-sequencing data also showed broad changes of H3K4me3 mark in the cells. Thus, HMGB1 in the nucleus dictates histone modifications. In conclusion, our study demonstrated a key role for HMGB1 in keratinocytes in the maintenance of chromatin modification status to protect from exuberant skin inflammation.
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Project description:Nrf2-dependent expression of numerous genes in Atg7-deficient livers was observed.
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Project description:Testing the consequences of the absence of the chromatin-associated HMGB1 protein on the transcriptome in Arabidopsis. Keywords: Comparison of mutant and wildtype samples. Four replicate RNA extractions were performed of each genotype using independent pools of plants. hmgb1#1 (Cy5) vs. Col-0#1 (Cy3) Col-0#2 (Cy5) vs. hmgb1#2 (Cy3) dye-swap hmgb1#3 (Cy5) vs. Col-0#3 (Cy3) Col-0#5 (Cy5) vs. hmgb1#4 (Cy3) dye-swap Samples were hybridized in two dye-swaps. The data were normalized over all 4 hybridizations to obtain one, single log-ratio(Sample/Reference). The raw data files of all four of the hybridizations are attached to the Sample.
2008-11-23 | E-GEOD-10638 | biostudies-arrayexpress
Project description:To unveil HMGB1 DNA occupancy in livers of mice after a metabolic stress either induced by a 12-week high fat diet consumption or a fasting (6hours)-refeeding (8hours) challenge. Challenges known to generate a robust activation of hepatic lipogenesis and liver steatosis.
2022-03-31 | E-MTAB-11543 | biostudies-arrayexpress
Project description:High Mobility Group Box 1 (HMGB1) is a highly abundant and evolutionarily conserved non-histone chromatin component with the ability to bind and bend DNA. The protein is involved in fundamental nuclear processes including nucleosome sliding, transcription, replication, V(D)J recombination and DNA transposition. To assess the functional impact of HMGB1 on transcription we performed gene expression profile analyses of mouse embryonic fibroblasts, wild-type or knockout for the Hmgb1 gene 2 genetic backgrounds: wild-type (Wt), Hmgb1-/- (KO), 3 biological replicates (rep1, rep2, rep3; S phase synchronized cells in duplicate only), no technical replicates. Each pair of wt and Hmgb1-/- MEFs was isolated from embryos born from a single Hmgb1+/- mother crossed with a Hmgb1 +/- male. Total RNAs from three pairs of MEFs, derived from three different mothers and cultured up to passage 3, were extracted using mirVana miRNA Isolation Kit (Ambion) and analyzed on the Illumina BeadsArray platform.
2013-10-01 | E-GEOD-18463 | biostudies-arrayexpress
Project description:Regenerative responses predispose tissues to tumor formation by largely unknown mechanisms. High-mobility group box 1 (HMGB1) is a danger-associated molecular pattern contributing to inflammatory pathologies. Here, we show that HMGB1 derived from keratinocytes, but not myeloid cells, delays cutaneous wound healing and drives skin tumor formation. In wounds of mice lacking HMGB1 selectively in keratinocytes, a marked reduction in neutrophil extracellular trap (NET) formation is observed. Pharmacological targeting of HMGB1 or NETs prevents skin tumorigenesis and accelerates wound regeneration. HMGB1-dependent NET formation and skin tumorigenesis is orchestrated by the cytokine TNF and requires RIPK1 kinase activity. NETs are present in the microenvironment of keratinocyte-derived tumors in mice and lesional and tumor skin of patients suffering from Recessive Dystrophic Epidermolysis Bullosa (RDEB), a disease in which skin blistering predisposes to tumorigenesis. We conclude that tumorigenicity of the wound microenvironment depends on epithelial-derived HMGB1 regulating NET formation, thereby establishing a mechanism linking reparative inflammation to tumor initiation.
2019-10-16 | GSE138918 | GEO
Project description:High Mobility Group Box 1 (HMGB1) is a highly abundant and evolutionarily conserved non-histone chromatin component with the ability to bind and bend DNA. The protein is involved in fundamental nuclear processes including nucleosome sliding, transcription, replication, V(D)J recombination and DNA transposition. To assess the functional impact of HMGB1 on transcription we performed gene expression profile analyses of HeLa cells stably transfected with an anti-HMGB1 shRNA expressing plasmid or a control plasmid. 2 stable clones: control HeLa, Hmgb1-knocked down HeLa, 3 technical replicates. Hmgb1 knockdown HeLa cells were prepared by stable transfection with the plasmid Hmgb1shRNA-pSuperior.puro or, as a mock control, with the empty vector pSuperior.puro (Invitrogen). Transfection was made starting from 500 thousands (500K) or 5 milions (5mil) cells. Transfected cells were selected with puromycin and single resistant clones were picked, amplified and analyzed for HMGB1 expression by western blot. A clone containing less then 10% of the wt amount of HMGB1 was selected for further experiments. Total RNAs were extracted using Quiagen RNeasy kit and analyzed on the Illumina BeadsArray platform in 2 technical replica (2 arrays).
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