Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells
| Autor: | Lucia Altucci, Amalia Forte, Marilena Cipollaro, Antonietta Coppola, Gilda Cobellis, Ciro Maione, Lucia Scisciola, Francesca Cuomo, Giuseppina Liguori, Chiara Botti, Ilaria Caiafa, Matilde Valeria Ursini, Umberto Galderisi |
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| Přispěvatelé: | Cuomo, Francesca, Coppola, Antonietta, Botti, Chiara, Maione, Ciro, Forte, Amalia, Scisciola, Lucia, Liguori, Giuseppina, Caiafa, Ilaria, Ursini, Matilde Valeria, Galderisi, Umberto, Cipollaro, Marilena, Altucci, Lucia, Cobellis, Gilda |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Stromal cell Pro-inflammatory cytokines lcsh:Medicine Inflammation Biology Article Proinflammatory cytokine Cell Line Epigenesis Genetic Histones 03 medical and health sciences Histone H3 0302 clinical medicine medicine Basic Helix-Loop-Helix Transcription Factors Animals Humans Epigenetics Rats Wistar lcsh:Science Author Correction Multidisciplinary Mesenchymal stem cell lcsh:R Mesenchymal Stem Cells DNA Methylation Cell biology Rats Histone Code Repressor Proteins Disease Models Animal 030104 developmental biology Hypoxia-inducible factors 030220 oncology & carcinogenesis Cytokines lcsh:Q medicine.symptom Stem cell Apoptosis Regulatory Proteins Transcription Factors |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) Scientific reports (Nature Publishing Group) 8 (2018). doi:10.1038/s41598-018-24221-5 info:cnr-pdr/source/autori:Cuomo F.; Coppola A.; Botti C.; Maione C.; Forte A.; Scisciola L.; Liguori G.; Caiafa I.; Ursini M.V.; Galderisi U.; Cipollaro M.; Altucci L.; Cobellis G./titolo:Pro-inflammatory cytokines activate hypoxia-inducible factor 3? via epigenetic changes in mesenchymal stromal%2Fstem cells/doi:10.1038%2Fs41598-018-24221-5/rivista:Scientific reports (Nature Publishing Group)/anno:2018/pagina_da:/pagina_a:/intervallo_pagine:/volume:8 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-24221-5 |
| Popis: | Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are influenced by low cell retention and survival in affected tissues, partially influenced by lesion’s microenvironment, where low oxygen conditions (i.e. hypoxia) and inflammation coexist. Hypoxia and inflammation are pathophysiological stresses, sharing common activators, such as hypoxia-inducible factors (HIFs) and NF-κB. HIF1α and HIF2α respond essentially to hypoxia, activating pathways involved in tissue repair. Little is known about the regulation of HIF3α. Here we investigated the role of HIF3α in vitro and in vivo. Human MSCs expressed HIF3α, differentially regulated by pro-inflammatory cytokines in an oxygen-independent manner, a novel and still uncharacterized mechanism, where NF-κB is critical for its expression. We investigated if epigenetic modifications are involved in HIF3α expression by methylation-specific PCR and histone modifications. Robust hypermethylation of histone H3 was observed across HIF3A locus driven by pro-inflammatory cytokines. Experiments in a murine model of arteriotomy highlighted the activation of Hif3α expression in infiltrated inflammatory cells, suggesting a new role for Hif3α in inflammation in vivo. |
| Databáze: | OpenAIRE |
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