ArticleLife science alliance2020
The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancer.
Article in Life science alliance, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Distinct colitis-associated macrophages drive NOD2-dependent bacterial sensing and gut homeostasis.The Journal of clinical investigation · 2025Article
- CANDiT: A machine learning framework for differentiation therapy in colorectal cancer.Cell reports. Medicine · 2025Article
- Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.Acta pharmaceutica Sinica. B · 2025Review
- A living organoid biobank of patients with Crohn's disease reveals molecular subtypes for personalized therapeutics.Cell reports. Medicine · 2024Article
- An Update onMicroorganisms · 2024Review
- The crosstalk between microbial sensors ELMO1 and NOD2 shape intestinal immune responses.Virulence · 2023Article
- The intestinal immune system and gut barrier function in obesity and ageing.The FEBS journal · 2023Review
- Treating Leaky Syndrome in the Over 65s: Progress and Challenges.Clinical interventions in aging · 2023Article
- Altered immunity to microbiota, B cell activation and depleted γδ/resident memory T cells in colorectal cancer.Cancer immunology, immunotherapy : CII · 2022Article
- SPT6 loss permits the transdifferentiation of keratinocytes into an intestinal fate that resembles Barrett's metaplasia.iScience · 2021Article
- Functional assays with human patient-derived enteroid monolayers to assess the human gut barrier.STAR protocols · 2021Article
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- Artificial intelligence guided discovery of a barrier-protective therapy in inflammatory bowel disease.Nature communications · 2021Article
- SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging.Molecular therapy. Nucleic acids · 2021Article
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- SPT6 promotes epidermal differentiation and blockade of an intestinal-like phenotype through control of transcriptional elongation.Nature communications · 2021Article
- Methionine Restriction Improves Gut Barrier Function by Reshaping Diurnal Rhythms of Inflammation-Related Microbes in Aged Mice.Frontiers in nutrition · 2021Article
- Modeling colorectal cancers using multidimensional organoids.Advances in cancer research · 2021Review
- The DNA Glycosylase NEIL2 SuppressesCells · 2020Article
- AMPK Activation Promotes Tight Junction Assembly in Intestinal Epithelial Caco-2 Cells.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
The gut barrier separates trillions of microbes from the largest immune system in the body; when compromised, a "leaky" gut barrier fuels systemic inflammation, which hastens the progression of chronic diseases. Strategies to detect and repair the leaky gut barrier remain urgent and unmet needs. Recently, a stress-polarity signaling (SPS) pathway has been described in which the metabolic sensor, AMP-kinase acts via its effector, GIV (also known as Girdin) to augment epithelial polarity exclusively under energetic stress and suppresses tumor formation. Using murine and human colon-derived organoids, and enteroid-derived monolayers (EDMs) that are exposed to stressors, we reveal that the SPS-pathway is active in the intestinal epithelium and requires a catalytically active AMP-kinase. Its pharmacologic augmentation resists stress-induced collapse of the epithelium when challenged with microbes or microbial products. In addition, the SPS-pathway is suppressed in the aging gut, and its reactivation in enteroid-derived monolayers reverses aging-associated inflammation and loss of barrier function. It is also silenced during progression of colorectal cancers. These findings reveal the importance of the SPS-pathway in the gut and highlights its therapeutic potential for treating gut barrier dysfunction in aging, cancer, and dysbiosis.
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Registered trials
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.