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Beta-7 integrin controls enterocyte migration in the small intestine

World Journal of Gastroenterology 2015年第6期21卷 1759-1764页

作者： Elke Kaemmerer paula kuhn Ursula Schneider Thomas Clahsen Min Kyung Jeon Christina Klaus Julia Andruszkow Michael Hrer Sabine Ernst Angela Schippers Norbert Wagner Nikolaus Gassler Institute of Pathology RWTH Aachen University Department of Pediatrics RWTH Aachen University Department of Medical Statistics RWTH Aachen University

AIM:To hypothesize that beta-7 integrin affects cellularmigration of both,lymphocytes and ***:The nucleoside analog Brd U was ip injected in beta-7-deficient mice(C57BL/6-Itgbtmlcgn/J)of male gender and age-matched male C57BL/J J mice(wild type)4,20,or 40 h before *** total small intestine was isolated,dissected,and used for morphometrical *** U-positive epithelial cells were numbered in at least 15 hemi-crypts per duodenum,jejunum,and ileum of each *** outer most Brd U-positive cell(cellmax)was determined per hemi-crypt,numerically documented,and statistically ***:Integrins containing the beta-7-chain were exclusively expressed on *** the small intestinal mucosa of beta-7 integrin-deficient mice the number of intraepithelial lymphocytes was drastically ***,the Peyer’s patches of beta-7integrin-deficient mice appeared *** beta-7integrin-deficient mice the location of cellmax was found in a higher position than it was the case for the *** difference was already detected at 4 h after Brd U application,but significantly increased with time(40 h after Brd U injection)in all small intestinal segments investigated,i.e.,duodenum,jejunum,and *** of small intestinal enterocytes was different between the experimental groups measured by cellmax ***:The E-cadherin beta-7 integrin pathway probably controls migration of enterocytes within the small intestinal surface lining epithelial layer.

关键词： Barrier function Cell migration Inflammatory bowel

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Intestinal genetic inactivation of caspase-8 diminishes migration of enterocytes

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World Journal of Gastroenterology 2015年第15期21卷 4499-4508页

作者： Elke Kaemmerer paula kuhn Ursula Schneider Min Kyung Jeon Christina Klaus Miriam Schiffer Danika Weisner Christian Liedtke J?rg J?kel Lieven Nils Kennes Ralf-Dieter Hilgers Norbert Wagner Nikolaus Gassler Institute of Pathology RWTH Aachen University Department of Pediatrics RWTH Aachen University Department of Medicine Ⅲ RWTH Aachen University Department of Medical Statistics RWTH Aachen University

AIM: To verify the hypothesis that caspase-8(Casp8), which regulates cellular apoptosis and necroptosis, is critically involved in enterocyte ***: Casp8-silenced Caco2 cells were used in migration assays. In addition, enterocyte-specific Casp8 heterozygous(Casp8+/?int) or homozygous knockout mice(Casp8?int) were generated by crossing genetically modified mice carrying lox P recombination sites in intron 2 and 4 of the murine Casp8 gene with transgenic animals expressing a cre-transgene under control of the villin promoter in a pure C57/BL6 genetic background. The nucleoside analog Brd U was injected i.p. in male Casp8+/?int and Casp8?int animals 4 h, 20 h, or 40 h before performing morphometric studies. Locations of anti-Brd U-immunostained cells(cellmax) in at least 50 hemi-crypts of 6 histoanatomically distinct intestinal mucosal regions were numbered and extracted for statistical procedures. For the mice cohort(n = 28), the walking distance of enterocytes was evaluated from cellmax within crypt(n = 57), plateau(n = 19), and villus(n = 172) positions, resulting in a total of 6838 observations. Data analysis was performed by fitting a three-level mixed effects modelto the ***: In cell culture experiments with Caco2 cells, Casp8 knockdown efficiency mediated by RNA interference on Casp8 transcripts was 80% controlled as determined by Western blotting. In the scratch assay, migration of Casp8-deleted Caco2 cells was significantly diminished when compared with controls(Casp8?scramble and Caco2). In Brd U-labeled Casp8?int mice, cellmax locations were found along the hemi-crypts in a lower position than it was for Casp8+/?int or control(cre-negative) animals. Statistical data analysis with a three-level mixed effects model revealed that in the six different intestinal locations(distinct segments of the small and large intestine), cell movement between the three mice groups differed widely. Especially in duodenal hemi-crypts, enterocyte movement w

关键词： Barrier function Caspase 8 Cell migration Inflammatory bowel disease Intestinal morphogenesis

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