Evidence map›Paper›PMID 25914458›Full record

ArticleWorld journal of gastroenterology2015

Intestinal genetic inactivation of caspase-8 diminishes migration of enterocytes.

Elke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Christian Liedtke, Jörg Jäkel, Lieven Nils Kennes and 3 more

Open access · hybridAbstract read
In one paragraph

Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Notch inhibition counteracts Paneth cell death in absence of caspase-8.Virchows Archiv : an international journal of pathology · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Elke KaemmererElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Paula KuhnElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Ursula SchneiderElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Min Kyung JeonElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Christina KlausElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Miriam SchifferElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Danika WeisnerElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Christian LiedtkeElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Jörg JäkelElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Lieven Nils KennesElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Ralf-Dieter HilgersElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Norbert WagnerElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
Nikolaus GasslerElke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Miriam Schiffer, Danika Weisner, Jörg Jäkel, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimTo verify the hypothesis that caspase-8 (Casp8), which regulates cellular apoptosis and necroptosis, is critically involved in enterocyte migration.

methodsCasp8-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 loxP 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 BrdU 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-BrdU-immunostained cells (cell(max)) 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 cell(max) 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 model to the data.

resultsIn 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 BrdU-labeled Casp8(∆int) mice, cell(max) 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 was different between the groups. At 20 h, duodenal cell(max) location was significantly lower in Casp8(∆int) (25.67 ± 2.49) than in Casp8(+/∆int) (35.67 ± 4.78; P < 0.05) or control littermates (44.33 ± 0.94; P < 0.01).

conclusionCasp8-dependent migration of enterocytes is likely involved in intestinal physiology and inflammation-related pathophysiology.

Indexed as

Cell MovementAnimalsCaco-2 CellsCaspase 8EnterocytesEnzyme RepressionGene Knockdown TechniquesGenotypeHumansInflammatory Bowel DiseasesIntestinesMice, Inbred C57BLMice, KnockoutPhenotypeRNA InterferenceSignal TransductionCASP8 protein, humanCasp8 protein, mouseCaspase 8Barrier functionCaspase 8Cell migrationInflammatory bowel diseaseIntestinal morphogenesis

Identifiers

PMID25914458
PMCPMC4402296
OpenAlexW2407377530

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.