ArticleThe Journal of clinical investigation2016
Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Temporal transcriptomic profiling identifies core regulators in cytokine-induced gut barrier disruption in differentiated Caco-2 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
- Integrated transcriptome and single-cell RNA sequencing identifies small GTPase-associated biomarkers in ulcerative colitis.Frontiers in immunology · 2026Article
- Advances in Understanding Intestinal Homeostasis: Lessons from Inflammatory Bowel Disease and Monogenic Intestinal Disorder Pathogenesis.International journal of molecular sciences · 2025Review
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling.Gut · 2024Article
- The epithelium takes the stage in asthma and inflammatory bowel diseases.Frontiers in cell and developmental biology · 2024Review
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- Role of Rho GTPases in inflammatory bowel disease.Cell death discovery · 2023Review
- Mechanisms of mucosal healing: treating inflammatory bowel disease without immunosuppression?Nature reviews. Gastroenterology & hepatology · 2022Review
- Impact of Epithelial Cell Shedding on Intestinal Homeostasis.International journal of molecular sciences · 2022Review
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- Review
- Editorial: Loss of Epithelial Barrier Integrity in Inflammatory Diseases: Cellular Mediators and Therapeutic Targets.Frontiers in medicine · 2021Article
- Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate.Nature communications · 2020Article
- Protective effects of oxymatrine against DSS-induced acute intestinal inflammation in mice via blocking the RhoA/ROCK signaling pathway.Bioscience reports · 2019Article
- Hobit- and Blimp-1-driven CD4Nature immunology · 2019Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although defects in intestinal barrier function are a key pathogenic factor in patients with inflammatory bowel diseases (IBDs), the molecular pathways driving disease-specific alterations of intestinal epithelial cells (IECs) are largely unknown. Here, we addressed this issue by characterizing the transcriptome of IECs from IBD patients using a genome-wide approach. We observed disease-specific alterations in IECs with markedly impaired Rho-A signaling in active IBD patients. Localization of epithelial Rho-A was shifted to the cytosol in IBDs, and inflammation was associated with suppressed Rho-A activation due to reduced expression of the Rho-A prenylation enzyme geranylgeranyltransferase-I (GGTase-I). Functionally, we found that mice with conditional loss of Rhoa or the gene encoding GGTase-I, Pggt1b, in IECs exhibit spontaneous chronic intestinal inflammation with accumulation of granulocytes and CD4+ T cells. This phenotype was associated with cytoskeleton rearrangement and aberrant cell shedding, ultimately leading to loss of epithelial integrity and subsequent inflammation. These findings uncover deficient prenylation of Rho-A as a key player in the pathogenesis of IBDs. As therapeutic triggering of Rho-A signaling suppressed intestinal inflammation in mice with GGTase-I-deficient IECs, our findings suggest new avenues for treatment of epithelial injury and mucosal inflammation in IBD patients.
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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.