GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis
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 i...
| Principais autores: | , , , , , , , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Cell Press
2022
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| _version_ | 1826314527503810560 |
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| author | Rana, N Privitera, G Kondolf, HC Bulek, K Lechuga, S De Salvo, C Corridoni, D Antanaviciute, A Maywald, RL Hurtado, AM Zhao, J Huang, EH Li, X Chan, ER Simmons, A Bamias, G Abbott, DW Heaney, JD Ivanov, AI Pizarro, TT |
| author_facet | Rana, N Privitera, G Kondolf, HC Bulek, K Lechuga, S De Salvo, C Corridoni, D Antanaviciute, A Maywald, RL Hurtado, AM Zhao, J Huang, EH Li, X Chan, ER Simmons, A Bamias, G Abbott, DW Heaney, JD Ivanov, AI Pizarro, TT |
| author_sort | Rana, N |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:35:27Z |
| format | Journal article |
| id | oxford-uuid:a97d958b-75a1-4798-80d3-513bbfe003d9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:35:27Z |
| publishDate | 2022 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:a97d958b-75a1-4798-80d3-513bbfe003d92024-09-16T16:14:45ZGSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a97d958b-75a1-4798-80d3-513bbfe003d9EnglishSymplectic ElementsCell Press2022Rana, NPrivitera, GKondolf, HCBulek, KLechuga, SDe Salvo, CCorridoni, DAntanaviciute, AMaywald, RLHurtado, AMZhao, JHuang, EHLi, XChan, ERSimmons, ABamias, GAbbott, DWHeaney, JDIvanov, AIPizarro, TTGasdermins 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. |
| spellingShingle | Rana, N Privitera, G Kondolf, HC Bulek, K Lechuga, S De Salvo, C Corridoni, D Antanaviciute, A Maywald, RL Hurtado, AM Zhao, J Huang, EH Li, X Chan, ER Simmons, A Bamias, G Abbott, DW Heaney, JD Ivanov, AI Pizarro, TT GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis |
| title | GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis |
| title_full | GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis |
| title_fullStr | GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis |
| title_full_unstemmed | GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis |
| title_short | GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis |
| title_sort | gsdmb is increased in ibd and regulates epithelial restitution repair independent of pyroptosis |
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