| Autor: |
Xiaoyan Yi, Bianca Marmontel de Souza, Toshiaki Sawatani, Florian Szymczak, Lorella Marselli, Piero Marchetti, Miriam Cnop, Decio L. Eizirik |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 25, Iss 11, Pp 105376- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2022.105376 |
| Popis: |
Summary: Target tissues of autoimmune and degenerative diseases show signals of inflammation. We used publicly available RNA-seq data to study whether pancreatic β-cells in type 1 and type 2 diabetes and neuronal tissue in multiple sclerosis and Alzheimer’s disease share inflammatory gene signatures. We observed concordantly upregulated genes in pairwise diseases, many of them related to signaling by interleukins and interferons. We next mined these signatures to identify therapies that could be re-purposed/shared among the diseases and identified the bromodomain inhibitors as potential perturbagens to revert the transcriptional signatures. We experimentally confirmed in human β-cells that bromodomain inhibitors I-BET151 and GSK046 prevent the deleterious effects of the pro-inflammatory cytokines interleukin-1β and interferon-γ and at least some of the effects of the metabolic stressor palmitate. These results demonstrate that key inflammation-induced molecular mechanisms are shared between β-cells and brain in autoimmune and degenerative diseases and that these signatures can be mined for drug discovery. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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