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Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation

ABSTRACT: Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation

PROVIDER: PRJNA577725 | ENA |

REPOSITORIES: ENA

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Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation

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

Transcription profiling of human peripheral blood neutrophils isolated from septic patients and treated in vitro with LPS or HMGB1

Project description:Peripheral blood neutrophils were isolated from septic patients and treated in vitro with LPS or HMGB1 Experiment Overall Design: 8 patients, each contributing a control, LPS-treated, and HMGB1-treated neutrophil sample.

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Comparison of the transcriptomes of hmgb1 vs Col-0

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

The effects of Hmgb1 depletion on gene expression in murine cells

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.

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Stimulation by LPS and HMGB1 in peripheral blood neutrophils from patients with sepsis-induced acute lung injury

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2006-08-01 | GSE3037 | GEO

Cold Temperature Delays Wound Healing in Postharvest Sugarbeet Roots.

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HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms.

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The effects of Hmgb1 depletion on gene expression in human cells

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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Constitutive overexpression of periostin delays wound healing in mouse skin.

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Receptor-Interacting Protein Kinase 3 Deficiency Delays Cutaneous Wound Healing.

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