TY - JOUR
TI - GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis
AU - Rana, N.
AU - Privitera, G.
AU - Kondolf, H.C.
AU - Bulek, K.
AU - Lechuga, S.
AU - De Salvo, C.
AU - Corridoni, D.
AU - Antanaviciute, A.
AU - Maywald, R.L.
AU - Hurtado, A.M.
AU - Zhao, J.
AU - Huang, E.H.
AU - Li, X.
AU - Chan, E.R.
AU - Simmons, A.
AU - Bamias, G.
AU - Abbott, D.W.
AU - Heaney, J.D.
AU - Ivanov, A.I.
AU - Pizarro, T.T.
JO - Cell Stem Cell
PY - 2022
VL - 185
TODO - 2
SP - 283-298.e17
PB - Elsevier B.V.
SN - 1934-5909
TODO - 10.1016/j.cell.2021.12.024
TODO - focal adhesion kinase;  GSDMB protein, human;  methotrexate;  pore forming cytotoxic protein;  transcriptome, case control study;  cell adhesion;  cell membrane;  cell motion;  cell proliferation;  drug effect;  epithelium cell;  genetics;  HEK293 cell line;  HT-29 cell line;  human;  inflammatory bowel disease;  metabolism;  mutation;  nucleotide sequence;  pathology;  phosphorylation;  pyroptosis;  reproducibility;  single nucleotide polymorphism;  upregulation;  wound healing, Base Sequence;  Case-Control Studies;  Cell Adhesion;  Cell Membrane;  Cell Movement;  Cell Proliferation;  Epithelial Cells;  Focal Adhesion Protein-Tyrosine Kinases;  HEK293 Cells;  HT29 Cells;  Humans;  Inflammatory Bowel Diseases;  Methotrexate;  Mutation;  Phosphorylation;  Polymorphism, Single Nucleotide;  Pore Forming Cytotoxic Proteins;  Pyroptosis;  Reproducibility of Results;  Transcriptome;  Up-Regulation;  Wound Healing
TODO - 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. © 2021 Elsevier Inc.
ER -