ArticleThe Journal of experimental medicine2010
Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 271 citations in OpenAlex.
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- ADAM17 and its proteolytic targets in disease pathogenesis.The FEBS journal · 2026Review
- Characterizing the Effects of Protein Glycosylation Perturbation on Phosphorylation Signaling.Analytical chemistry · 2026Article
- Transferrin receptor 1 shedding by the pro-inflammatory iRhom-ADAM17 complex and ADAM10 regulates cellular iron uptake and ferroptosis.Experimental & molecular medicine · 2026Article
- Structure, mechanism and clinical relevance of NRG1 fusions in cancer.Journal of biomedical science · 2026Review
- Discovery of FLF-15 as a novel selective inhibitor of ADAM17 to prevent hepatocellular carcinoma metastasis.Molecular diversity · 2026Article
- Characterizing the Effects of Protein Glycosylation Perturbation on Phosphorylation Signaling.bioRxiv : the preprint server for biology · 2025Article
- Myeloid ADAM17 induces ST2Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Structural insights into the activation and inhibition of the ADAM17-iRhom2 complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ligustilide Suppresses Macrophage-Mediated Intestinal Inflammation and Restores Gut Barrier via EGR1-ADAM17-TNF-α Pathway in Colitis Mice.Research (Washington, D.C.) · 2025Article
- A Valuable Target for Therapy: The Metalloproteinase ADAM10.Current protein & peptide science · 2025Review
- Review
- Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis.Inflammatory bowel diseases · 2024Review
- Understanding very early onset inflammatory bowel disease (VEOIBD) in relation to inborn errors of immunity.Immunological reviews · 2024Review
- Role of Metalloproteinases in Diabetes-associated Mild Cognitive Impairment.Current neuropharmacology · 2024Review
- Are peptidomimetics the compounds of choice for developing new modulators of the JAK-STAT pathway?Frontiers in immunology · 2024Review
- ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?International journal of molecular sciences · 2023Review
- The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth.Life science alliance · 2023Article
- Role of Muscarinic Acetylcholine Receptors in Intestinal Epithelial Homeostasis: Insights for the Treatment of Inflammatory Bowel Disease.International journal of molecular sciences · 2023Review
- CD200 ectodomain shedding into the tumor microenvironment leads to NK cell dysfunction and apoptosis.The Journal of clinical investigation · 2022Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protease a disintegrin and metalloprotease (ADAM) 17 cleaves tumor necrosis factor (TNF), L-selectin, and epidermal growth factor receptor (EGF-R) ligands from the plasma membrane. ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer. ADAM17-deficient mice are not viable. Conditional ADAM17 knockout models demonstrated proinflammatory activities of ADAM17 in septic shock via shedding of TNF. We used a novel gene targeting strategy to generate mice with dramatically reduced ADAM17 levels in all tissues. The resulting mice called ADAM17(ex/ex) were viable, showed compromised shedding of ADAM17 substrates from the cell surface, and developed eye, heart, and skin defects as a consequence of impaired EGF-R signaling caused by failure of shedding of EGF-R ligands. Unexpectedly, although the intestine of unchallenged homozygous ADAM17(ex/ex) mice was normal, ADAM17(ex/ex) mice showed substantially increased susceptibility to inflammation in dextran sulfate sodium colitis. This was a result of impaired shedding of EGF-R ligands resulting in failure to phosphorylate STAT3 via the EGF-R and, consequently, in defective regeneration of epithelial cells and breakdown of the intestinal barrier. Besides regulating the systemic availability of the proinflammatory cytokine TNF, our results demonstrate that ADAM17 is needed for vital regenerative activities during the immune response. Thus, our mouse model will help investigate ADAM17 as a potential drug target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.