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Series GSE159695 Query DataSets for GSE159695
Status Public on Jan 01, 2021
Title Protective role of HMGB1 in keratinocytes in skin inflammation
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
 
Overall design We analyzed keratinocytes from WT and K5-HMGB1 male mice. Keratinocytes were left untreated or treated with rIL-4 for 12 hours. Total RNA was extracted and analyzed by the Affymetrix Clariom S Array, Mouse. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.
 
Contributor(s) Senda N, Yanai H
Citation(s) 33443188
Submission date Oct 20, 2020
Last update date Apr 02, 2021
Contact name Hideyuki Yanai
E-mail(s) yanai@inflammology.rcast.u-tokyo.ac.jp
Phone 81-3-5452-6491
Organization name University of Tokyo
Street address Komaba 4-6-1
City Meguro-ku
State/province Tokyo
ZIP/Postal code 153-0041
Country Japan
 
Platforms (1)
GPL23038 [Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay)
Samples (4)
GSM4837751 WT keratinocytes_IL-4(-)
GSM4837752 KO keratinocytes_IL-4(-)
GSM4837753 WT keratinocytes_IL-4(+)
Relations
BioProject PRJNA670207

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE159695_RAW.tar 4.9 Mb (http)(custom) TAR (of CEL, CHP)
GSE159695_WT_IL4_minus_vs_IL4_plus.xlsx 186.9 Kb (ftp)(http) XLSX
GSE159695_WT_IL4_plus_vs_KO_IL4_plus.xlsx 70.2 Kb (ftp)(http) XLSX
Processed data provided as supplementary file
Processed data included within Sample table
Processed data are available on Series record

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