Proteomics

Dataset Information

0

Beta 1 integrin signaling governs necroptosis via the chromatin remodeling factor CHD4


ABSTRACT: Fibrosis, characterized by sustained activation of myofibroblasts and excessive extracellular matrix (ECM) deposition, is known to be associated with chronic inflammation. RIPK3, a key kinase mediating TNF-driven necroptosis signaling, is upregulated in fibrosis and contributes to the TNF-mediated inflammation. In bile duct ligation-induced liver fibrosis, we found that myofibroblasts are the major cell type expressing RIPK3. Genetic ablation of beta1 integrins, the major profibrotic ECM receptors in fibroblasts, not only abolished ECM fibrillogenesis but also blunted RIPK3 expression via an epigenetic mechanism mediated by the chromatin remodeling factor CHD4. While the function of CHD4 has been conventionally linked to NuRD and ChAHP complexes, we found that CHD4 potently repressed a set of genes, including Ripk3, with high locus specificity but independent of either the NuRD or ChAHP complex. Thus, our data uncover that beta1 integrin intrinsically links fibrotic signaling to RIPK3-driven inflammation via a novel mode of action of CHD4.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Barbara Steigenberger  

LAB HEAD: Veit Hornung

PROVIDER: PXD041505 | Pride | 2023-10-30

REPOSITORIES: Pride

Similar Datasets

2023-10-23 | GSE229795 | GEO
2016-08-18 | E-MTAB-4810 | biostudies-arrayexpress
2019-07-01 | E-MTAB-7298 | biostudies-arrayexpress
2010-03-23 | E-GEOD-15205 | biostudies-arrayexpress
2018-11-07 | GSE114389 | GEO
2016-07-18 | E-GEOD-83253 | biostudies-arrayexpress
2014-08-18 | E-GEOD-57758 | biostudies-arrayexpress
2010-03-11 | GSE15205 | GEO
2019-02-05 | GSE123726 | GEO
2014-02-21 | E-GEOD-55206 | biostudies-arrayexpress