Guanylin and uroguanylin are produced by mouse intestinal epithelial cells of columnar and secretory lineage

Ikpa, Pauline T.; Sleddens, Hein F.B.M.; Steinbrecher, Kris A.; Peppelenbosch, Maikel P.; Jonge, Hugo R. de; Smits, Ron; Bijvelds, Marcel J. C.

doi:10.1007/s00418-016-1453-4

Cited by 38 publications

(39 citation statements)

References 54 publications

(88 reference statements)

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“…4). The distal ileum may be a region where both guanylin and uroguanylin are expressed to comparable levels (22), and interestingly, the transcript levels of both the ligands were reduced on infection in both Gucy2c ϩ/ϩ and Gucy2c Ϫ/Ϫ mice ( Fig. 4).…”

Section: Fig 1 Gucy2cmentioning

confidence: 93%

Absence of Receptor Guanylyl Cyclase C Enhances Ileal Damage and Reduces Cytokine and Antimicrobial Peptide Production during Oral Salmonella enterica Serovar Typhimurium Infection

et al. 2018

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Nontyphoidal disease contributes toward significant morbidity and mortality across the world. Host factors, including gamma interferon, tumor necrosis factor alpha, and gut microbiota, significantly influence the outcome of pathogenesis. However, the entire repertoire of host protective mechanisms contributing to pathogenicity is not completely appreciated. Here, we investigated the roles of receptor guanylyl cyclase C (GC-C), which is predominantly expressed in the intestine and regulates intestinal cell proliferation and fluid-ion homeostasis. Mice deficient in GC-C () displayed accelerated mortality compared with that for wild-type mice following infection via the oral route, even though both groups possessed comparable systemic infection burdens. Survival following intraperitoneal infection remained similar in both groups, indicating that GC-C offered protection via a gut-mediated response. The serum cortisol level was higher in mice than wild-type () mice, and an increase in infection-induced thymic atrophy with a loss of immature CD4 CD8 double-positive thymocytes was observed. Accelerated and enhanced damage in the ileum, including submucosal edema, epithelial cell damage, focal tufting, and distortion of the villus architecture, was seen in mice concomitantly with a larger number of ileal tissue-associated bacteria. Transcription of key mediators of-induced inflammation (interleukin-22/Reg3β) was altered in mice in comparison to that in mice. A reduction in fecal lactobacilli, which are protective against infection, was observed in mice. mice cohoused with wild-type mice continued to show reduced amounts of lactobacilli and increased susceptibility to infection. Our study, therefore, suggests that the receptor GC-C confers a survival advantage during gut-mediated serovar Typhimurium pathogenesis, presumably by regulating effector mechanisms and maintaining a beneficial microbiome.

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Section: Fig 1 Gucy2cmentioning

confidence: 93%

Absence of Receptor Guanylyl Cyclase C Enhances Ileal Damage and Reduces Cytokine and Antimicrobial Peptide Production during Oral Salmonella enterica Serovar Typhimurium Infection

et al. 2018

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“…Exogenous STa is a molecular mimic of two endogenous peptide ligands, which also function as GUCY2C agonists. These ligands, guanylin (GUCA2A) and uroguanylin (GUCA2B), both expressed in gut epithelial cells[ 15 , 35 , 36 ], act locally as autocrine and paracrine hormones to regulate GUCY2C signaling and fluid and electrolyte homeostasis[ 28 , 31 ]. Additionally, uroguanylin acts as an endocrine hormone, secreted into the systemic circulation postprandially to activate hypothalamic GUCY2C and induce satiety[ 37 - 39 ].…”

Section: Intestinal Homeostatic Maintenance By the Gucy2c Signaling Amentioning

confidence: 99%

Guanylyl cyclase C signaling axis and colon cancer prevention

Pattison¹,

Merlino²,

Blomain³

2016

WJG

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Colorectal cancer (CRC) is a major cause of cancer-related mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C (GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells, plays an important role in orchestrating intestinal homeostatic mechanisms. These effects are mediated by the endogenous hormones guanylin (GUCA2A) and uroguanylin (GUCA2B), which bind and activate GUCY2C to regulate proliferation, metabolism and barrier function in intestine. Recent studies have demonstrated a link between GUCY2C silencing and intestinal dysfunction, including tumorigenesis. Indeed, GUCY2C silencing by the near universal loss of its paracrine hormone ligands increases colon cancer susceptibility in animals and humans. GUCY2C’s role as a tumor suppressor has opened the door to a new paradigm for CRC prevention by hormone replacement therapy using synthetic hormone analogs, such as the FDA-approved oral GUCY2C ligand linaclotide (Linzess™). Here we review the known contributions of the GUCY2C signaling axis to CRC, and relate them to a novel clinical strategy targeting tumor chemoprevention.

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“…4). The distal ileum may be a region where both guanylin and uroguanylin are expressed to comparable levels (22), and interestingly, transcript levels of both the ligands were reduced on infection in both Gucy2c +/+ and Gucy2c -/- mice (Fig. 4).…”

Section: Resultsmentioning

confidence: 99%

Absence of receptor guanylyl cyclase C enhances ileal damage and reduces cytokine and antimicrobial peptide production during oralSalmonellaTyphimurium infection

Majumdar

Mishra

Nandi

et al. 2017

Preprint

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Guanylin and uroguanylin are produced by mouse intestinal epithelial cells of columnar and secretory lineage

Cited by 38 publications

References 54 publications

Absence of Receptor Guanylyl Cyclase C Enhances Ileal Damage and Reduces Cytokine and Antimicrobial Peptide Production during Oral Salmonella enterica Serovar Typhimurium Infection

Absence of Receptor Guanylyl Cyclase C Enhances Ileal Damage and Reduces Cytokine and Antimicrobial Peptide Production during Oral Salmonella enterica Serovar Typhimurium Infection

Guanylyl cyclase C signaling axis and colon cancer prevention

Absence of receptor guanylyl cyclase C enhances ileal damage and reduces cytokine and antimicrobial peptide production during oralSalmonellaTyphimurium infection

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