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:Background: We previously identified that high-mobility group box-1 (HMGB1) is increased and undergoes post-translational modifications (PTMs) in response to alcohol consumption. Here we hypothesized that specific PTMs, occurring mostly in hepatocytes and myeloid cells, could contribute to the pathogenesis of alcohol-associated liver disease (AALD). Methods: We used the Lieber-DeCarli (LDC) model of early alcohol-induced liver injury, combined with engineered viral vectors and genetic approaches to regulate the expression of HMGB1, its PTMs (reduced [H], oxidized [O], acetylated [Ac], both [O+Ac]), and its receptors (RAGE, TLR4) in a cell-specific manner (hepatocytes and/or myeloid cells). Results: Hmgb1 ablation in hepatocytes or myeloid cells partially protected, while ablation in both prevented steatosis, inflammation, IL1B production, and alcohol-induced liver injury. Hepatocytes were a major source of [H], [O], and [Ac] HMGB1, whereas myeloid cells produced only [H] and [Ac] HMGB1. Neutralization of HMGB1 prevented, whereas injection of [H] HMGB1 increased AALD, which was worsened by injection of [O] HMGB1. While [O] HMGB1 induced liver injury, [Ac] HMGB1 protected and counteracted the effects of [O] HMGB1 in AALD. [O] HMGB1 stimulated macrophage (MF) migration, activation, IL1B production and secretion. Ethanol-fed RageΔMye but not Tlr4ΔMye, RageΔHep, or Tlr4ΔHep mice were protected from AALD, indicating a crucial role of RAGE in myeloid cells for AALD. [O] HMGB1 recruited and activated myeloid cells through RAGE and contributed to steatosis, inflammation, and IL1B production in AALD. Conclusion: These results provide evidence for targeting [O] HMGB1 of hepatocyte origin as a ligand for RAGE signaling in myeloid cells and a driver of steatosis, inflammatory cell infiltration, and IL1B production in AALD. Importantly, we reveal that [Ac] HMGB1 offsets the noxious effects of [O] HMGB1 in AALD.
2024-09-28 | GSE278350 | 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.
2021-01-01 | GSE159695 | GEO
Project description:Nrf2-dependent expression of numerous genes in Atg7-deficient livers was observed.
2016-06-21 | GSE65174 | GEO
Project description:During inflammation and tissue regeneration, the alarmin High Mobility Group Box 1 (HMGB1), in its reduced isoform, enhances the activity of the chemokine CXCL12, forming a heterocomplex that acts via the chemokine receptor CXCR4. Despite the established roles of both HMGB1 and CXCL12 in tumor progression and metastatic spread to distal sites, the role of the CXCL12/HMGB1 heterocomplex in cancer has never been investigated. By employing a newly established mass spectrometry protocol that allows an unambiguous distinction between reduced (red HMGB1) and oxidized (ox HMGB1) HMGB1 isoforms in cell lysates, we demonstrate that human epithelial cells derived from breast (MCF-7 and MDA-MB-231) and prostate (PC-3) cancer predominantly express red-HMGB1, while primary CD3+ T lymphocytes from peripheral blood express both HMGB1 isoforms. All these cancer cells release HMGB1 in the extracellular microenvironment together with varying concentrations of thioredoxin and thioredoxin reductase. The CXCL12/HMGB1 heterocomplex enhances, via CXCR4, the directional migration and invasiveness of cancer cells characterized by high metastatic potential that possess a fully active thioredoxin system, contributing to maintain red-HMGB1. On the contrary, cancer cells with low metastatic potential, lack thioredoxin reductase, promptly uptake CXCL12 and fail to respond to the heterocomplex. Our study demonstrates that the responsiveness of cancer cells to the CXCL12/HMGB1 heterocomplex, resulting in enhanced cell migration and invasiveness, depends on the maintenance of HMGB1 in its reduced isoform, and suggests disruption of the heterocomplex as a potential therapeutic target to inhibit invasion and metastatic spread in cancer therapies.
2024-05-02 | PXD048091 | Pride
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