ArticleJCI insight2023
Epithelial Gab1 calibrates RIPK3-dependent necroptosis to prevent intestinal inflammation.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 10 citations in OpenAlex.
- [Methyl syringate alleviates DSS-induced colitis in mice by suppressing intestinal epithelial cell apoptosisNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- The dual role of RIPK family in IBD: from cell death to therapeutic targeting.Molecular medicine (Cambridge, Mass.) · 2026Review
- [Poricoic acid A alleviates dextran sulfate sodium-induced colitis in mice by regulating AMPK/mTOR-mediated autophagy and inhibiting intestinal epithelial cell apoptosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Epithelial Gab1 Restricts Sepsis-Induced Intestinal Injury by Orchestrating TNF/NF-κB Axis.Mediators of inflammation · 2026Article
- Effects ofFrontiers in microbiology · 2026Article
- Structure-based design of potent and selective inhibitors targeting RIPK3 for eliminating on-target toxicity in vitro.Nature communications · 2025Article
- CRIF1 gene therapy ameliorates inflammatory bowel disease by suppressing TH17 cells and fibrosis through mitochondrial function regulation.Frontiers in immunology · 2025Article
- An immunohistochemical atlas of necroptotic pathway expression.EMBO molecular medicine · 2024Article
- Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024Review
- 2'-Hydroxycinnamaldehyde Alleviates Intestinal Inflammation by Attenuating Intestinal Mucosal Barrier Damage Via Directly Inhibiting STAT3.Inflammatory bowel diseases · 2024Article
- Cell Death, by Any Other Name….Cells · 2024Review
- Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a hallmark of inflammatory bowel disease (IBD), elevated intestinal epithelial cell (IEC) death compromises the gut barrier, activating the inflammatory response and triggering more IEC death. However, the precise intracellular machinery that prevents IEC death and breaks this vicious feedback cycle remains largely unknown. Here, we report that Grb2-associated binder 1 (Gab1) expression is decreased in patients with IBD and inversely correlated with IBD severity. Gab1 deficiency in IECs accounted for the exacerbated colitis induced by dextran sodium sulfate owing to sensitizing IECs to receptor-interaction protein kinase 3-mediated (RIPK3-mediated) necroptosis, which irreversibly disrupted the homeostasis of the epithelial barrier and promoted intestinal inflammation. Mechanistically, Gab1 negatively regulated necroptosis signaling through inhibiting the formation of RIPK1/RIPK3 complex in response to TNF-α. Importantly, administration of RIPK3 inhibitor revealed a curative effect in epithelial Gab1-deficient mice. Further analysis indicated mice with Gab1 deletion were prone to inflammation-associated colorectal tumorigenesis. Collectively, our study defines a protective role for Gab1 in colitis and colitis-driven colorectal cancer by negatively regulating RIPK3-dependent necroptosis, which may serve as an important target to address necroptosis and intestinal inflammation-related disease.
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Registered trials
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