Advanced search
1 file | 4.33 MB Add to list

Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state

Author
Organization
Project
Abstract
Apoptosis is widely believed to be crucial for epithelial cell death and shedding in the intestine, thereby shaping the overall architecture of the gastrointestinal tract, but also regulating tolerance induction, pinpointing a role of apoptosis intestinal epithelial cell (IEC) turnover and maintenance of barrier function, and in maintaining immune homeostasis. To experimentally address this concept, we generated IEC-specific knockout mice that lack both executioner caspase-3 and caspase-7 (Casp3/7ΔIEC), which are the converging point of the extrinsic and intrinsic apoptotic pathway. Surprisingly, the overall architecture, cellular landscape, and proliferation rate remained unchanged in these mice. However, nonapoptotic cell extrusion was increased in Casp3/7ΔIEC mice, compensating apoptosis deficiency, maintaining the same physiological level of IEC shedding. Microbiome richness and composition stayed unaffected, bearing no sign of dysbiosis. Transcriptome and single-cell RNA sequencing analyses of IECs and immune cells revealed no differences in signaling pathways of differentiation and inflammation. These findings demonstrate that during homeostasis, apoptosis per se is dispensable for IEC turnover at the top of intestinal villi intestinal tissue dynamics, microbiome, and immune cell composition.
Keywords
Multidisciplinary, mucosal immunology, apoptosis, caspases, cell death, regeneration, PROGRAMMED CELL-DEATH, STEM-CELLS, APOPTOTIC CELLS, INFLAMMATION, FADD, DIFFERENTIATION, PROLIFERATION, MUTATIONS, NECROSIS, CLEAVAGE

Downloads

  • 4725 22Ghazavi.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 4.33 MB

Citation

Please use this url to cite or link to this publication:

MLA
Ghazavi, Farzaneh, et al. “Executioner Caspases 3 and 7 Are Dispensable for Intestinal Epithelium Turnover and Homeostasis at Steady State.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 119, no. 6, 2022, doi:10.1073/pnas.2024508119.
APA
Ghazavi, F., Huysentruyt, J., De Coninck, J., Kourula, S., Martens, S., Hassannia, B., … Vandenabeele, P. (2022). Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119(6). https://doi.org/10.1073/pnas.2024508119
Chicago author-date
Ghazavi, Farzaneh, Jelle Huysentruyt, Jordy De Coninck, Stephanie Kourula, Sofie Martens, Behrouz Hassannia, Tim Wartewig, et al. 2022. “Executioner Caspases 3 and 7 Are Dispensable for Intestinal Epithelium Turnover and Homeostasis at Steady State.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119 (6). https://doi.org/10.1073/pnas.2024508119.
Chicago author-date (all authors)
Ghazavi, Farzaneh, Jelle Huysentruyt, Jordy De Coninck, Stephanie Kourula, Sofie Martens, Behrouz Hassannia, Tim Wartewig, Tatyana Divert, Ria Roelandt, Bastian Popper, Andreas Hiergeist, Peter Tougaard, Tom Vanden Berghe, Marie Joossens, Geert Berx, Nozomi Takahashi, Adam Wahida, and Peter Vandenabeele. 2022. “Executioner Caspases 3 and 7 Are Dispensable for Intestinal Epithelium Turnover and Homeostasis at Steady State.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119 (6). doi:10.1073/pnas.2024508119.
Vancouver
1.
Ghazavi F, Huysentruyt J, De Coninck J, Kourula S, Martens S, Hassannia B, et al. Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2022;119(6).
IEEE
[1]
F. Ghazavi et al., “Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state,” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 119, no. 6, 2022.
@article{8742892,
  abstract     = {{Apoptosis is widely believed to be crucial for epithelial cell death and shedding in the intestine, thereby shaping the overall architecture of the gastrointestinal tract, but also regulating tolerance induction, pinpointing a role of apoptosis intestinal epithelial cell (IEC) turnover and maintenance of barrier function, and in maintaining immune homeostasis. To experimentally address this concept, we generated IEC-specific knockout mice that lack both executioner caspase-3 and caspase-7 (Casp3/7ΔIEC), which are the converging point of the extrinsic and intrinsic apoptotic pathway. Surprisingly, the overall architecture, cellular landscape, and proliferation rate remained unchanged in these mice. However, nonapoptotic cell extrusion was increased in Casp3/7ΔIEC mice, compensating apoptosis deficiency, maintaining the same physiological level of IEC shedding. Microbiome richness and composition stayed unaffected, bearing no sign of dysbiosis. Transcriptome and single-cell RNA sequencing analyses of IECs and immune cells revealed no differences in signaling pathways of differentiation and inflammation. These findings demonstrate that during homeostasis, apoptosis per se is dispensable for IEC turnover at the top of intestinal villi intestinal tissue dynamics, microbiome, and immune cell composition.}},
  articleno    = {{e2024508119}},
  author       = {{Ghazavi, Farzaneh and Huysentruyt, Jelle and De Coninck, Jordy and Kourula, Stephanie and Martens, Sofie and Hassannia, Behrouz and Wartewig, Tim and Divert, Tatyana and Roelandt, Ria and Popper, Bastian and Hiergeist, Andreas and Tougaard, Peter and Vanden Berghe, Tom and Joossens, Marie and Berx, Geert and Takahashi, Nozomi and Wahida, Adam and Vandenabeele, Peter}},
  issn         = {{0027-8424}},
  journal      = {{PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}},
  keywords     = {{Multidisciplinary,mucosal immunology,apoptosis,caspases,cell death,regeneration,PROGRAMMED CELL-DEATH,STEM-CELLS,APOPTOTIC CELLS,INFLAMMATION,FADD,DIFFERENTIATION,PROLIFERATION,MUTATIONS,NECROSIS,CLEAVAGE}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{11}},
  title        = {{Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state}},
  url          = {{http://doi.org/10.1073/pnas.2024508119}},
  volume       = {{119}},
  year         = {{2022}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: