ArticleInflammatory bowel diseases2012
Cyclic AMP dysregulates intestinal epithelial cell restitution through PKA and RhoA.
Article in Inflammatory bowel diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Human-induced Pluripotent Stem Cell-derived Gut Organoids Recapitulate Regional Specific Genetic Programs and a Role for cAMP in Lineage Specification.Cellular and molecular gastroenterology and hepatology · 2025Article
- Decoding the mosaic of inflammatory bowel disease: Illuminating insights with single-cell RNA technology.Computational and structural biotechnology journal · 2024Review
- Ectopically Localized Epithelial Cell Clumps in Ulcers Are Derived from Reserved Crypt Stem Cells in a Mouse Model of Ulcerative Colitis.Digestive diseases and sciences · 2022Article
- Contribution of the Immune Response in the Ileum to the Development of Diarrhoea caused by Helminth Infection: Studies with the Sheep Model.Functional & integrative genomics · 2022Article
- PRKAR2A deficiency protects mice from experimental colitis by increasing IFN-stimulated gene expression and modulating the intestinal microbiota.Mucosal immunology · 2021Article
- H89 Treatment Reduces Intestinal Inflammation andMicroorganisms · 2020Article
- An in vivo RNAi screen uncovers the role of AdoR signaling and adenosine deaminase in controlling intestinal stem cell activity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The impact of the rs8005161 polymorphism on G protein-coupled receptor GPR65 (TDAG8) pH-associated activation in intestinal inflammation.BMC gastroenterology · 2019Article
- Rainbow Trout (Frontiers in immunology · 2019Article
- Synergistic effect of phosphodiesterase 4 inhibitor and serum on migration of endotoxin-stimulated macrophages.Innate immunity · 2018Article
- Responses of rainbow trout intestinal epithelial cells to different kinds of nutritional deprivation.Fish physiology and biochemistry · 2018Article
- Plasma Asprosin Concentrations Are Increased in Individuals with Glucose Dysregulation and Correlated with Insulin Resistance and First-Phase Insulin Secretion.Mediators of inflammation · 2018Article
- [Phosphodiesterase 4 inhibition for treatment of endothelial barrier and microcirculation disorders in sepsis].Der Anaesthesist · 2017Review
- A Role for cAMP and Protein Kinase A in Experimental Necrotizing Enterocolitis.The American journal of pathology · 2017Article
- Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7.Nature genetics · 2017Article
- Article
- Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells.Molecular carcinogenesis · 2015Article
- The unrecognized effects of phosphodiesterase 4 on epithelial cells in pulmonary inflammation.PloS one · 2015Article
- HEK-293 cells expressing the cystic fibrosis transmembrane conductance regulator (CFTR): a model for studying regulation of Cl- transport.Physiological reports · 2014Article
- Small GTPases of the Ras superfamily regulate intestinal epithelial homeostasis and barrier function via common and unique mechanisms.Tissue barriers · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMucosal homeostasis is dependent on the establishment and maintenance of the cell-cell contacts that comprise the physiological barrier. Breaks in the barrier are linked to multiple diseases such as inflammatory bowel disease. While increased cyclic adenosine monophosphate (cAMP) levels limit inflammation by decreasing leukocyte infiltration, the effects of elevated cAMP on intestinal epithelial repair are unknown.
methodsRestitution in animals administered rolipram was monitored by microscopic examination after laser wounding of the intestinal epithelium or in mice treated with dextran sodium sulfate (DSS). In vitro analysis was conducted using IEC6 and T84 cells to determine the role of elevated cAMP in altering Rho-dependent cellular migration signaling pathways.
resultsWe show that treatment with rolipram, forskolin, and cAMP analogs decrease intestinal epithelial cell migration in vitro. In vivo cell imaging revealed that increased cAMP resulted in a decreased cellular migration rate, with cells at the edge displaying the highest activity. As expected, elevated cAMP elicited increased protein kinase A (PKA) activity, in turn resulting in the inactivation and sequestration of RhoA and decreased actin reorganization. The ablation of restitution by cAMP was not restricted to cell culture, as forskolin and rolipram treatment significantly decreased epithelial microwound closure induced by the two photon confocal injury model.
conclusionsTogether, these data suggest that administration of cAMP-elevating agents paradoxically decrease infiltration of damage-causing leukocytes while also preventing epithelial repair and barrier maintenance. We propose that treatment with cAMP-elevating agents severely limits mucosal reepithelialization and should be contraindicated for use in chronic inflammatory bowel disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.