Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease
Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflamma...
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MDPI AG,
2023-12-01T00:00:00Z.
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|---|---|---|---|
| 001 | doaj_abfb784285c4493a974a1b061d07b5b5 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Flores Martín-Reyes |e author |
| 700 | 1 | 0 | |a Manuel Bernal |e author |
| 700 | 1 | 0 | |a Cristina Rodríguez-Díaz |e author |
| 700 | 1 | 0 | |a Damaris Rodríguez-de los Reyes |e author |
| 700 | 1 | 0 | |a Ailec Ho-Plagaro |e author |
| 700 | 1 | 0 | |a Francisca Rodríguez-Pacheco |e author |
| 700 | 1 | 0 | |a Laura Camacho-Martel |e author |
| 700 | 1 | 0 | |a Raquel Camargo-Camero |e author |
| 700 | 1 | 0 | |a Francisco J. Rodríguez-González |e author |
| 700 | 1 | 0 | |a Guillermo Alcain-Martínez |e author |
| 700 | 1 | 0 | |a Rafael Martín-Masot |e author |
| 700 | 1 | 0 | |a Víctor M. Navas-López |e author |
| 700 | 1 | 0 | |a Marina Villanueva-Paz |e author |
| 700 | 1 | 0 | |a María Isabel Lucena |e author |
| 700 | 1 | 0 | |a Eduardo García-Fuentes |e author |
| 700 | 1 | 0 | |a Carlos López-Gómez |e author |
| 245 | 0 | 0 | |a Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease |
| 260 | |b MDPI AG, |c 2023-12-01T00:00:00Z. | ||
| 500 | |a 10.3390/antiox12122105 | ||
| 500 | |a 2076-3921 | ||
| 520 | |a Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPR<sup>mt</sup>) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPR<sup>mt</sup>, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPR<sup>mt</sup> pathway in the pathophysiology of Crohn's disease. | ||
| 546 | |a EN | ||
| 690 | |a non-steroidal anti-inflammatory drugs | ||
| 690 | |a inflammatory bowel diseases | ||
| 690 | |a Crohn's disease | ||
| 690 | |a mitochondria | ||
| 690 | |a mitochondrial unfolded protein response | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Antioxidants, Vol 12, Iss 12, p 2105 (2023) | |
| 787 | 0 | |n https://www.mdpi.com/2076-3921/12/12/2105 | |
| 787 | 0 | |n https://doaj.org/toc/2076-3921 | |
| 856 | 4 | 1 | |u https://doaj.org/article/abfb784285c4493a974a1b061d07b5b5 |z Connect to this object online. |