Evidence map›Paper›PMID 33847777›Full record

ArticleArchives of toxicology2021

Mechanisms of deoxynivalenol-induced endocytosis and degradation of tight junction proteins in jejunal IPEC-J2 cells involve selective activation of the MAPK pathways.

Enkai Li, Nathan Horn, Kolapo M Ajuwon

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In one paragraph

Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 63 citations in OpenAlex.

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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

3 authors at 2 institutions in 1 country.

Enkai LiDepartment of Animal Sciences, Purdue University, 270 S. Russell St., West Lafayette, IN, 47907-2041, USA.
Nathan HornUnited Animal Health, 322 S Main St #1113, Sheridan, IN, 46069, USA.
Kolapo M AjuwonDepartment of Animal Sciences, Purdue University, 270 S. Russell St., West Lafayette, IN, 47907-2041, USA. kajuwon@purdue.edu.ORCID http://orcid.org/0000-0002-5523-7457
Purdue University West Lafayette · USUnited Animal Health (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mycotoxin contamination in foods is a major risk factor for human and animal health due to its prevalence in cereals and their by-products. Deoxynivalenol (DON), mainly produced by Fusarium genera, is the most common mycotoxin detected in cereal products. Deoxynivalenol disrupts intestinal barrier function and decreases protein levels of tight junction proteins (TJP). However, the overall mechanism by which DON regulates specific TJP turnover and epithelial cell integrity remains unclear. Herein, we show that DON (2 μM) decreases the protein stability and accelerates the degradation of TJP in the lysosome. Interestingly, pretreatment of cells with dynasore (a dynamin-dependent endocytosis inhibitor) protected against DON-induced degradation of claudin-3 and 4. Immunofluorescence analysis also shows that the decreased membrane presence of claudin-4 and ZO-1 induced by DON is reversible with dynamin inhibition, whereas the pretreatment with cytochalasin D (an actin-dependent endocytosis inhibitor) reverses the degradation of claudin-1 and 4 induced by DON. We also show that the endocytosis and degradation of claudin-1 is regulated by p38 mitogen-activated protein kinase (MAPK), whereas the endocytosis of claudin-4 and ZO-1 is mediated by c-Jun-N-terminal kinase (JNK). Resveratrol, with JNK inhibitory activity, also prevents the endocytosis and degradation of claudin-4 and ZO-1 and protects against DON-induced decrease in transepithelial electrical resistance (TEER) and increase in FITC-dextran permeability. Collectively, this study, for the first time, shows that DON accelerates the endocytosis and degradation of TJP and this is regulated by the activation of p38 MAPK and JNK signaling pathways. Therefore, natural bioactive compounds with p38 MAPK and JNK inhibitory activities may be effective in preventing the DON-induced TJP disruption and preserve gut barrier function in vivo.

Indexed as

AnimalsCell LineEndocytosisJejunumMAP Kinase Signaling Systemp38 Mitogen-Activated Protein KinasesPermeabilityProtein StabilitySwineTight Junction ProteinsTrichothecenesdeoxynivalenolp38 Mitogen-Activated Protein KinasesTight Junction ProteinsTrichothecenesDeoxynivalenolEndocytosisLysosomeMAPKTight junction

Identifiers

PMID33847777
OpenAlexW3155057443

What OpenQuestion holds

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Registered trials

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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.