title: Guanylin and uroguanylin are produced by mouse intestinal epithelial cells of columnar and secretory lineage.
abstract: Guanylin (GN) and uroguanylin (UGN), through activation of guanylyl cyclase C (GCC), serve to control intestinal fluid homeostasis. Both peptides are produced in the intestinal epithelium, but their cellular origin has not been fully charted. Using quantitative PCR and an improved in situ hybridization technique (RNAscope), we have assessed the expression of GN (Guca2a), UGN (Guca2b), and GCC (Gucy2c) in mouse intestine. In the crypts of Lieberkühn, expression of Guca2a and Guca2b was restricted to cells of secretory lineage, at the crypt's base, and to a region above, previously identified as a common origin of cellular differentiation. In this compartment, comparatively uniform levels of Guca2a and Guca2b expression were observed throughout the length of the gut. In contrast, Guca2a and Guca2b expression in the villus-surface region was more variable, and reflected the distinct, but overlapping expression pattern observed previously. Accordingly, in jejunum and ileum, Guca2a and Guca2b were abundantly expressed by enterocytes, whereas in colon only Guca2a transcript was found in the surface region. In duodenum, only low levels of Guca2b transcript were observed in columnar cells, and Guca2a expression was restricted entirely to cells of the secretory lineage. Gucy2c was shown to be expressed relatively uniformly along the rostrocaudal and crypt-villus axes and was also found in the duodenal glands. Our study reveals novel aspects of the cellular localization of the GCC signaling axis that, apart from its role in the regulation of fluid balance, link it to pH regulation, cell cycle control, and host defense.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Pauline T
authors.initials: PT
authors.lastname: Ikpa
authors.affiliation: Department of Pathology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Hein F B M
authors.initials: HF
authors.lastname: Sleddens
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
authors.forename: Kris A
authors.initials: KA
authors.lastname: Steinbrecher
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Hugo R
authors.initials: HR
authors.lastname: de Jonge
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: Smits
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. m.bijvelds@erasmusmc.nl.
authors.forename: Marcel J C
authors.initials: MJ
authors.lastname: Bijvelds
mesh_terms: D000818:Animals; D019070:Cell Lineage; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D051379:Mice; D008815:Mice, Inbred Strains; D045265:Natriuretic Peptides / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; C072685:guanylin; C084362:uroguanylin
keywords: Cyclic guanosine monophosphate; Enteroendocrine cells; Guanylyl cyclase C; Intestinal fluid transport