Mucin muc2 deficiency and weaning influences the expression of the innate defense genes reg3ß, reg3¿ and angiogenin-4
| Autor: | Jerry M. Wells, Maria van der Sluis, Isabelle Van Seuningen, Anita M. Korteland-van Male, Nanda Burger-van Paassen, Peng Lu, Ingrid B. Renes, Adrianus C. J. M. de Bruijn, Jan Dekker, Janneke Witte-Bouma, Linda M. P. Loonen, Johannes B. van Goudoever |
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| Přispěvatelé: | Pediatric surgery, ICaR - Circulation and metabolism, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Wageningen University and Research [Wageningen] (WUR), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Paediatrics |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
epithelial-cells Mouse bactericidal lectin Gene Expression lcsh:Medicine Pancreatitis-Associated Proteins Mucin 2 [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity Mice 0302 clinical medicine Intestinal mucosa Gene expression Molecular Cell Biology Intestine Small Intestinal Mucosa lcsh:Science Regulation of gene expression Mice Knockout 0303 health sciences Multidisciplinary Animal Models respiratory system Innate Immunity medicine.anatomical_structure 030220 oncology & carcinogenesis Medicine Goblet Cells gastrointestinal-tract Research Article Angiogenin Colon Immunology In situ hybridization Gastroenterology and Hepatology Biology digestive system Molecular Genetics 03 medical and health sciences Model Organisms human-milk [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] medicine Animals Gene Regulation paneth cells Host-Microbe Interactomics 030304 developmental biology Inflammation Mucin-2 necrotizing enterocolitis inflammatory-bowel-disease Mucin lcsh:R Immunity Computational Biology Proteins Ribonuclease Pancreatic Molecular biology Small intestine Immunity Innate digestive system diseases interleukin-10-deficient mice lectin regiii-gamma Gene Expression Regulation WIAS Clinical Immunology Muramidase lcsh:Q soluble cd14 |
| Zdroj: | PLoS ONE, 7(6) PLoS ONE, Vol 7, Iss 6, p e38798 (2012) PLoS ONE, 7(6):e38798. Public Library of Science PLoS ONE Burger-van Paassen, N, Loonen, L M P, Witte-Bouma, J, Korteland-van Male, A M, de Bruijn, A C J M, van der Sluis, M, Lu, P, van Goudoever, J B, Wells, J M, Dekker, J, van Seuningen, I & Renes, I B 2012, ' Mucin Muc2 Deficiency and Weaning Influences the Expression of the Innate Defense Genes Reg3 beta, Reg3 gamma and Angiogenin-4 ', PLoS ONE, vol. 7, no. 6, e38798 . https://doi.org/10.1371/journal.pone.0038798 PLoS ONE, Public Library of Science, 2012, 7 (6), pp.e38798. ⟨10.1371/journal.pone.0038798⟩ PLoS ONE 7 (2012) 6 PLoS ONE, 2012, 7 (6), pp.e38798. ⟨10.1371/journal.pone.0038798⟩ PLoS ONE, 7(6). Public Library of Science |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0038798 |
| Popis: | International audience; Background: Mucin Muc2 is the structural component of the intestinal mucus layer. Absence of Muc2 leads to loss of this layer allowing direct bacterial-epithelial interactions. We hypothesized that absence of the mucus layer leads to increased expression of innate defense peptides. Specifically, we aimed to study the consequence of Muc2 deficiency (Muc2−/−) on the expression of regenerating islet-derived protein 3 beta (Reg3β), regenerating islet-derived protein 3 gamma (Reg3γ), and angiogenin-4 (Ang4) in the intestine shortly before and after weaning.Methods: Intestinal tissues of Muc2−/− and wild-type (WT) mice were collected at postnatal day 14 (P14, i.e. pre-weaning) and P28 (i.e. post-weaning). Reg3β, Reg3γ, and Ang4 expression was studied by quantitative real-time PCR, Western-blot, in situ hybridization, and immunohistochemistry.Results: Reg3β and Reg3γ were expressed by diverging epithelial cell types; namely enterocytes, Paneth cells, and goblet cells. Additionally, Ang4 expression was confined to Paneth cells and goblet cells. Expression of Reg3β, Reg3γ, and Ang4 differed between WT and Muc2−/− mice before and after weaning. Interestingly, absence of Muc2 strongly increased Reg3β and Reg3γ expression in the small intestine and colon. Finally, morphological signs of colitis were only observed in the distal colon of Muc2−/− mice at P28, where and when expression levels of Reg3β, Reg3γ, and Ang4 were the lowest.Conclusions: Expression of Reg3 proteins and Ang4 by goblet cells point to an important role for goblet cells in innate defense. Absence of Muc2 results in up-regulation of Reg3β and Reg3γ expression, suggesting altered bacterial-epithelial signaling and an innate defense response in Muc2−/− mice. The inverse correlation between colitis development and Reg3β, Reg3γ, and Ang4 expression levels might point toward a role for these innate defense peptides in regulating intestinal inflammation. |
| Databáze: | OpenAIRE |
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