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Xie, W.* ; Wyckaert, L.* ; Vadi, M.* ; Verstraeten, B.* ; Divert, T.* ; Haerinck, J.* ; De Rycke, R.* ; Baeke, F.* ; Lamkanfi, M.* ; Berx, G.* ; Wahida, A. ; Vandenabeele, P.*

Caspase-3/7 deficiency results in enhanced intestinal inflammation and reduced tumorigenesis.

Sci. Adv. 12:eadz5906 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Aberrant intestinal epithelial cell (IEC) death is common in inflammatory bowel disease (IBD) and related animal models. While various cell death pathways contribute to disease, the dominant modalities and their regulatory mechanisms in intestinal inflammation remain ill defined. Using the DSS colitis model, we examined the contribution of apoptosis (Casp3/7ΔIEC), necroptosis (MlklΔIEC), pyroptosis (GsdmeΔIEC, Gsdmd-/-), and ferroptosis (Gpx4iΔIEC) in IECs. Mice lacking caspase-3/7 in IECs showed worsened colitis, higher mortality, and impaired regeneration, not seen in the other transgenic mice. Caspase-3/7 deficiency in IECs hindered stem cell proliferation and increased inflammatory cell death, disrupting barrier integrity and delaying recovery. Despite heightened inflammation, Casp3/7ΔIEC mice had reduced tumor formation in the AOM/DSS-induced colorectal cancer model. These findings highlight a protective role for caspase-3/7 in controlling inflammation and tissue regeneration, while promoting tumorigenesis following intestinal injury, and suggest modulation of caspase-3/7 as a promising therapeutic strategy in IBD and colorectal cancer.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gasdermin D; Colorectal-cancer; Cell-death; Apoptosis; Necroptosis; Ferroptosis; Instability; Activation; Pyroptosis; Resolution
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 12, Heft: 12, Seiten: , Artikelnummer: eadz5906 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Metabolism and Cell Death (MCD)
Förderungen Ghent University
Excellence of Science research consortium
UGent Special Research Fund Methusalem
Interuniversity BOF projects
Foundation against Cancer
Research Foundation-Flanders