ArticlePloS one2011
Loss of guanylyl cyclase C (GCC) signaling leads to dysfunctional intestinal barrier.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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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.
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Who cites it
58 citing papers in PubMed, 88 citations in OpenAlex.
- BEST4⁺ cells: a potential hub of intestinal ion transport and diarrhea manipulation.Advanced biotechnology · 2026Review
- The impact of rumen and hindgut microbiomes on the persistent productivity of long-lived dairy cows.Microbiome · 2026Article
- Gut reactions and gut instincts: regulation of intestinal homeostasis by receptor guanylyl cyclase C (GC-C).The Biochemical journal · 2025Review
- Bioinformatics analysis-based mining of potential markers for inflammatory bowel disease and their immune relevance.Translational cancer research · 2024Article
- Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis.Inflammatory bowel diseases · 2024Review
- Article
- Microbiota-derived butyrate dampens linaclotide stimulation of the guanylate cyclase C pathway in patient-derived colonoids.Neurogastroenterology and motility · 2023Article
- A phase I, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C.Cancer chemotherapy and pharmacology · 2023Article
- The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation.Animal models and experimental medicine · 2022Article
- Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer.Personalized medicine · 2022Review
- Type-2 cGMP-dependent protein kinase suppresses proliferation and carcinogenesis in the colon epithelium.Carcinogenesis · 2022Article
- In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids ofMolecules (Basel, Switzerland) · 2021Article
- [Changes of guanylate cyclase C in colon tissues of rats with intestinal injury associated with severe acute pancreatitis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer.Expert review of clinical pharmacology · 2020Review
- The protective effects of XH-105 against radiation-induced intestinal injury.Journal of cellular and molecular medicine · 2019Article
- Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn's disease.Therapeutic advances in gastroenterology · 2019Article
- Profile of plecanatide in the treatment of chronic idiopathic constipation: design, development, and place in therapy.Clinical and experimental gastroenterology · 2019Review
- Effects of Maillard-type caseinate glycation on the preventive action of caseinate digests in acrylamide-induced intestinal barrier dysfunction in IEC-6 cells.RSC advances · 2018Article
- Effects of Thymoquinone on radiation enteritis in mice.Scientific reports · 2018Article
- Linaclotide Attenuates Visceral Organ Crosstalk: Role of Guanylate Cyclase-C Activation in Reversing Bladder-Colon Cross-Sensitization.The Journal of pharmacology and experimental therapeutics · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGuanylyl Cyclase C (GCC) signaling via uroguanylin (UGN) and guanylin activation is a critical mediator of intestinal fluid homeostasis, intestinal cell proliferation/apoptosis, and tumorigenesis. As a mechanism for some of these effects, we hypothesized that GCC signaling mediates regulation of intestinal barrier function. METHODOLOGY/PRINCIPAL
findingsParacellular permeability of intestinal segments was assessed in wild type (WT) and GCC deficient (GCC-/-) mice with and without lipopolysaccharide (LPS) challenge, as well as in UGN deficient (UGN-/-) mice. IFNγ and myosin light chain kinase (MLCK) levels were determined by real time PCR. Expression of tight junction proteins (TJPs), phosphorylation of myosin II regulatory light chain (MLC), and STAT1 activation were examined in intestinal epithelial cells (IECs) and intestinal mucosa. The permeability of Caco-2 and HT-29 IEC monolayers, grown on Transwell filters was determined in the absence and presence of GCC RNA interference (RNAi). We found that intestinal permeability was increased in GCC-/- and UGN-/- mice compared to WT, accompanied by increased IFNγ levels, MLCK and STAT1 activation in IECs. LPS challenge promotes greater IFNγ and STAT1 activation in IECs of GCC-/- mice compared to WT mice. Claudin-2 and JAM-A expression were reduced in GCC deficient intestine; the level of phosphorylated MLC in IECs was significantly increased in GCC-/- and UGN-/- mice compared to WT. GCC knockdown induced MLC phosphorylation, increased permeability in IEC monolayers under basal conditions, and enhanced TNFα and IFNγ-induced monolayer hyperpermeability. CONCLUSIONS/SIGNIFICANCE: GCC signaling plays a protective role in the integrity of the intestinal mucosal barrier by regulating MLCK activation and TJ disassembly. GCC signaling activation may therefore represent a novel mechanism in maintaining the small bowel barrier in response to injury.
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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.