Projecten per jaar
Description
Expression profiling by high throughput sequencing: mus musculus
Abstract
Acinar cell dedifferentiation is one of the most notable features of acute and chronic pancreatitis. It can also be the initial step that facilitates pancreatic cancer development. In the present study, we further decipher the precise mechanism and regulation using murine experimental models. Our RNAseq analysis indicates that, early acinar cell dedifferentiation is accompanied by multiple pathways related to cell survival that are highly enriched, and where SLC7A11 (xCT) is transiently upregulated. xCT is the specific subunit of the cystine/glutamate antiporter system xC-. Acinar cells with depleted or reduced xCT function show an increase in ferroptosis relating to lipid peroxidation. Lower glutathione levels and more lipid ROS accumulation could be rescued by the antioxidant N-acetylcysteine or the ferroptosis inhibitor Ferrostatin-1. In caerulein-induced acute pancreatitis in mice, xCT also prevents lipid peroxidation in acinar cells. In conclusion, during stress, acinar cell fate seems to be poised for avoiding several forms of cell death. xCT specifically prevents acinar cell ferroptosis by fueling the glutathione pool and maintaining ROS balance. The data suggest that xCT offers a druggable tipping point to steer the acinar cell fate in stress conditions.
Size
8.8Mb
Datum van beschikbaarheid | 7 aug 2023 |
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Uitgever | Gene Expression Omnibus (GEO) |
Datum van data-aanmaak | 7 aug 2023 |
Format
- Format
Projecten
- 1 Afgelopen
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FWOAL931: Acinaire cel-specifieke vatbaarheid voor tumorontwikkeling in de pancreas: de kritische regulatoren als mogelijk doelwit voor therapie
1/01/19 → 31/12/22
Project: Fundamenteel
Onderzoekersoutput
- 1 Article
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Pancreatic acinar cell fate relies on system xC- to prevent ferroptosis during stress
Pan, Z., Van den Bossche, J-L., Rodriguez-Aznar, E., Janssen, P., Lara, O., Ates, G., Massie, A., De Paep, D. L., Houbracken, I., Mambretti, M. & Rooman, I., 21 aug 2023, In: Cell & Death Disease. 14, 8, 10 blz., 536.Onderzoeksoutput: Article › peer review
Open AccessBestand7 Citaten (Scopus)26 Downloads (Pure)