BACKGROUND & AIMS: Expression of mucin MUC2, the structural component of the colonic mucus layer, is lowered in inflammatory bowel disease. Our aim was to obtain insight in the role of Muc2 in epithelial protection. METHODS: Muc2 knockout (Muc2(-/-)) and Muc2 heterozygous (Muc2(+/-)) mice were characterized and challenged by a colitis-inducing agent, dextran sulfate sodium (DSS). We monitored clinical symptoms, intestinal morphology, and differences in intestine-specific protein and messenger RNA levels. RESULTS: The Muc2(-/-) mice showed clinical signs of colitis (as of 5 weeks), aggravating as the mice aged. Microscopic analysis of the colon of Muc2(-/-) mice showed mucosal thickening, increased proliferation, and superficial erosions. Colonic goblet cells in the Muc2(-/-) mice were negative for Muc2, but trefoil factor 3 was still detectable. In Muc2(-/-) mice, transient de novo expression of Muc6 messenger RNA was observed in the distal colon. On day 2 of DSS treatment, the histologic damage was more severe in Muc2(+/-) versus wild-type (Muc2(+/+)) mice, but the disease activity index was not yet different. By day 7, the disease activity index and histologic score were significantly elevated in Muc2(+/-) versus Muc2(+/+) mice. The disease activity index of the Muc2(-/-) mice was higher (versus both Muc2(+/+) and Muc2(+/-) mice) throughout DSS treatment. The histologic damage in the DSS-treated Muc2(-/-) mice was different compared with Muc2(+/+) and Muc2(+/-) mice, with many crypt abscesses instead of mucosal ulcerations. CONCLUSIONS: This study shows that Muc2 deficiency leads to inflammation of the colon and contributes to the onset and perpetuation of experimental colitis.
BACKGROUND & AIMS: Expression of mucin MUC2, the structural component of the colonic mucus layer, is lowered in inflammatory bowel disease. Our aim was to obtain insight in the role of Muc2 in epithelial protection. METHODS:Muc2 knockout (Muc2(-/-)) and Muc2 heterozygous (Muc2(+/-)) mice were characterized and challenged by a colitis-inducing agent, dextran sulfate sodium (DSS). We monitored clinical symptoms, intestinal morphology, and differences in intestine-specific protein and messenger RNA levels. RESULTS: The Muc2(-/-) mice showed clinical signs of colitis (as of 5 weeks), aggravating as the mice aged. Microscopic analysis of the colon of Muc2(-/-) mice showed mucosal thickening, increased proliferation, and superficial erosions. Colonic goblet cells in the Muc2(-/-) mice were negative for Muc2, but trefoil factor 3 was still detectable. In Muc2(-/-) mice, transient de novo expression of Muc6 messenger RNA was observed in the distal colon. On day 2 of DSS treatment, the histologic damage was more severe in Muc2(+/-) versus wild-type (Muc2(+/+)) mice, but the disease activity index was not yet different. By day 7, the disease activity index and histologic score were significantly elevated in Muc2(+/-) versus Muc2(+/+) mice. The disease activity index of the Muc2(-/-) mice was higher (versus both Muc2(+/+) and Muc2(+/-) mice) throughout DSS treatment. The histologic damage in the DSS-treated Muc2(-/-) mice was different compared with Muc2(+/+) and Muc2(+/-) mice, with many crypt abscesses instead of mucosal ulcerations. CONCLUSIONS: This study shows that Muc2 deficiency leads to inflammation of the colon and contributes to the onset and perpetuation of experimental colitis.
Authors: Moshe Biton; Avi Levin; Michal Slyper; Irit Alkalay; Elad Horwitz; Hagar Mor; Sharon Kredo-Russo; Tali Avnit-Sagi; Gady Cojocaru; Farid Zreik; Zvi Bentwich; Matthew N Poy; David Artis; Michael D Walker; Eran Hornstein; Eli Pikarsky; Yinon Ben-Neriah Journal: Nat Immunol Date: 2011-01-30 Impact factor: 25.606
Authors: Jenny K Gustafsson; Anna Ermund; Malin E V Johansson; André Schütte; Gunnar C Hansson; Henrik Sjövall Journal: Am J Physiol Gastrointest Liver Physiol Date: 2011-12-08 Impact factor: 4.052
Authors: Malin E V Johansson; Daniel Ambort; Thaher Pelaseyed; André Schütte; Jenny K Gustafsson; Anna Ermund; Durai B Subramani; Jessica M Holmén-Larsson; Kristina A Thomsson; Joakim H Bergström; Sjoerd van der Post; Ana M Rodriguez-Piñeiro; Henrik Sjövall; Malin Bäckström; Gunnar C Hansson Journal: Cell Mol Life Sci Date: 2011-09-25 Impact factor: 9.261
Authors: Thaddeus S Stappenbeck; John D Rioux; Atsushi Mizoguchi; Tatsuya Saitoh; Alan Huett; Arlette Darfeuille-Michaud; Tom Wileman; Noboru Mizushima; Simon Carding; Shizuo Akira; Miles Parkes; Ramnik J Xavier Journal: Autophagy Date: 2011-04-01 Impact factor: 16.016
Authors: Sergei I Grivennikov; Kepeng Wang; Daniel Mucida; C Andrew Stewart; Bernd Schnabl; Dominik Jauch; Koji Taniguchi; Guann-Yi Yu; Christoph H Osterreicher; Kenneth E Hung; Christian Datz; Ying Feng; Eric R Fearon; Mohamed Oukka; Lino Tessarollo; Vincenzo Coppola; Felix Yarovinsky; Hilde Cheroutre; Lars Eckmann; Giorgio Trinchieri; Michael Karin Journal: Nature Date: 2012-11-08 Impact factor: 49.962