Journal article
GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis
- Abstract:
- Gasdermins are a family of structurally related proteins originally described for their role in pyroptosis. Gasdermin B (GSDMB) is currently the least studied, and while its association with genetic susceptibility to chronic mucosal inflammatory disorders is well established, little is known about its functional relevance during active disease states. Herein, we report increased GSDMB in inflammatory bowel disease, with single-cell analysis identifying epithelial specificity to inflamed colonocytes/crypt top colonocytes. Surprisingly, mechanistic experiments and transcriptome profiling reveal lack of inherent GSDMB-dependent pyroptosis in activated epithelial cells and organoids but instead point to increased proliferation and migration during in vitro wound closure, which arrests in GSDMB-deficient cells that display hyper-adhesiveness and enhanced formation of vinculin-based focal adhesions dependent on PDGF-A-mediated FAK phosphorylation. Importantly, carriage of disease-associated GSDMB SNPs confers functional defects, disrupting epithelial restitution/repair, which, altogether, establishes GSDMB as a critical factor for restoration of epithelial barrier function and the resolution of inflammation.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Publisher copy:
- 10.1016/j.cell.2021.12.024
Authors
+ NIHR Academy
More from this funder
- Funder identifier:
- https://ror.org/02nv4he32
- Grant:
- NIHR-RP-R3-12-026
+ National Institute for Health Research
More from this funder
- Funder identifier:
- https://ror.org/0187kwz08
- Grant:
- NIHR201410
+ Wellcome Trust
More from this funder
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 102974/Z/13/Z
- 102974/Z/13/Z
- 219523/Z/19/Z
+ Medical Research Council
More from this funder
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MC_PC_MR/S025952/1
+ UK Research and Innovation
More from this funder
- Funder identifier:
- https://ror.org/001aqnf71
- Grant:
- MR/S036377/1
- Publisher:
- Cell Press
- Journal:
- Cell More from this journal
- Volume:
- 185
- Issue:
- 2
- Pages:
- 283-298
- Place of publication:
- United States
- Publication date:
- 2022-01-11
- Acceptance date:
- 2021-12-16
- DOI:
- EISSN:
-
1097-4172
- ISSN:
-
0092-8674
- Pmid:
-
35021065
- Language:
-
English
- Pubs id:
-
1232733
- Local pid:
-
pubs:1232733
- Deposit date:
-
2024-09-13
- ARK identifier:
Terms of use
- Copyright holder:
- Elsevier Inc.
- Copyright date:
- 2021
- Rights statement:
- © 2021 Elsevier Inc.
- Notes:
-
A correction to the article is available online at: https://doi.org/10.1016/j.cell.2024.01.010
The final version of this article is available under an Elsevier user license at: https://doi.org/10.1016/j.cell.2021.12.024
If you are the owner of this record, you can report an update to it here: Report update to this record