| Experiment Id | E-GEOD-79590 | Series Id | GSE79590 |
| Name | Keratins control Nrf2 by regulating mitochondrial activity and barrier composition / Keratin-dependent TSLP expression suggests a link between skin blistering and atopic disease | Experiment Type | transcription profiling by array |
| Study Type | WT vs. Mutant | Source | ArrayExpress |
| Curation Date | 2019-03-21 |
| description | The epidermal barrier protects the body against mechanical injury, infection and dehydration. The respective contribution of type I and type II keratins which form the major cytoskeleton in epidermal keratinocytes in barrier formation and stress protection is incompletely understood. Here, we reveal a novel mechanism by which keratins control anti-oxidant responses through barrier-dependent and cell-autonomous mechanisms. Mice lacking the entire type I (KtyI) or type II (KtyII) keratin gene clusters suffer from distinct prenatal barrier defects. Comparative transcriptome profiling identifies essential cornified envelope components and reveals strong upregulation of the bZIP transcription factor Nrf2 in situ. Isolated keratinocytes from both strains of mice show elevated mitochondrial oxygen consumption and Nrf2 activity, decreased upon keratin re-expression. We propose a model in which keratins control mitochondria-derived oxidative stress via Nrf2 activation. Our findings reveal major contributions of keratins to chronic inflammation and autoimmune disorders. Total RNA obtained from E18.5 embryo back skin from type I and II keratin knockout compared with respective wild type. |
