Evidence map›Paper›PMID 34162953›Full record

ArticleScientific reports2021

Hypoxia and heat stress affect epithelial integrity in a Caco-2/HT-29 co-culture.

Puqiao Lian, Saskia Braber, Soheil Varasteh, Harry J Wichers, Gert Folkerts

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
10.5field-weighted citation impact, top 1% 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

41 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. A simple, efficient technique to make colon crypt gels for 3D models.3D printing and additive manufacturing · 2025
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Heat Stress Influences Immunity ThroughAnimals : an open access journal from MDPI · 2025
    Article
  18. Review
  19. Oxidative Stress by HAntioxidants (Basel, Switzerland) · 2025
    Article
  20. 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

5 authors at 2 institutions in 1 country.

Puqiao LianDivision of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
Saskia BraberDivision of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
Soheil VarastehDivision of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
Harry J WichersFood and Biobased Research, Wageningen University and Research, Wageningen, The Netherlands.
Gert FolkertsDivision of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands. g.folkerts@uu.nl.
Utrecht University · NLWageningen University & Research · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia and hyperthermia, which can be induced by high environmental temperature or strenuous exercise, are two common stressors that affect intestinal epithelial integrity and lead to multiple clinical symptoms. In this study, we developed an in-vitro intestinal monolayer model using two human colonic epithelial cell lines, Caco-2 and HT-29, co-cultured in Transwell inserts, and investigated the effects of heat treatment and/or hypoxia on the epithelial barrier function. The monolayer with a ratio of 9:1 (Caco-2:HT-29) showed high trans-epithelial electrical resistance (TEER), low Lucifer Yellow permeability and high mucin production. Hyperthermia and/or hypoxia exposure (2 h) triggered heat shock and oxidative stress responses. HSP-70 and HSF-1 protein levels were up-regulated by hyperthermia, which were further enhanced when hyperthermia was combined with hypoxia. Increased HIF-1α protein expression and Nrf2 nuclear translocation was only caused by hypoxia. Hyperthermia and/or hypoxia exposure disrupted the established monolayer by increasing paracellular permeability, decreasing ZO-1, claudin-3 and occludin protein/mRNA expression, while enhancing E-cadherin protein expression. Tight junction protein distribution in the monolayer was also modulated by the hyperthermia and/or hypoxia exposure. In addition, transcription levels of mucin genes, MUC-2 and MUC-5AC, were increased after 2 h of hyperthermia and/or hypoxia exposure. In conclusion, this Caco-2/HT-29 cell model is valid and effective for studying detrimental effects of hyperthermia and/or hypoxia on intestinal barrier function and related heat shock and oxidative stress pathways and can be used to investigate possible interventions to reverse hyperthermia and/or hypoxia-induced intestinal epithelial injury.

Indexed as

Cell HypoxiaHeat-Shock ResponseAdenocarcinomaAdenocarcinoma, MucinousCell Line, TumorCoculture TechniquesColonic NeoplasmsColoring AgentsElectric ImpedanceEnterocytesGene Expression Regulation, NeoplasticGoblet CellsHumansIntercellular JunctionsIsoquinolinesMucinsColoring AgentsIsoquinolineslucifer yellowMucinsNeoplasm ProteinsRNA, MessengerRNA, Neoplasm

Identifiers

PMID34162953
PMCPMC8222227
OpenAlexW3174419684

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.