Evidence map›Paper›PMID 36219473›Full record

ArticleJournal of Crohn's & colitis2023

Autophagy Reduces the Degradation and Promotes Membrane Localization of Occludin to Enhance the Intestinal Epithelial Tight Junction Barrier against Paracellular Macromolecule Flux.

Kushal Saha, Ashwinkumar Subramenium Ganapathy, Alexandra Wang, Nathan Michael Morris, Eric Suchanec, Wei Ding, Gregory Yochum, Walter Koltun, Meghali Nighot, Thomas Ma and 1 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Journal of Crohn's & colitis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

40 citing papers in PubMed, 57 citations in OpenAlex.

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  16. Biological Modulation of Autophagy by Nanoplastics: A Current Overview.International journal of molecular sciences · 2025
    Review
  17. Article
  18. Macronutrients as Regulators of Intestinal Epithelial Permeability: Where Do We Stand?Comprehensive reviews in food science and food safety · 2025
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Kushal SahaDivision of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.ORCID 0000-0003-2692-2532
Ashwinkumar Subramenium GanapathyDivision of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.ORCID 0000-0001-5254-9431
Alexandra WangDivision of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Nathan Michael MorrisDivision of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.ORCID 0000-0001-9988-9951
Eric SuchanecDivision of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Wei DingDivision of Colon and Rectal Surgery, Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Gregory YochumDivision of Colon and Rectal Surgery, Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Walter KoltunDivision of Colon and Rectal Surgery, Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Meghali NighotDivision of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Thomas MaDivision of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Prashant NighotDivision of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.ORCID 0000-0003-2368-7290
Pennsylvania State University · US

Funding

Unfolded Protein Response and Autophagy in T Helper Cell Effector FunctionP20GM121176 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI VOJO P DERETIC · 2017 to 2026
$24.9M
Intestinal Barrier, Probiotic Bacteria, and the Gut-Liver AxisR01DK121073 · NIDDK · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI MA, THOMAS Y · 2019 to 2023
$2.4M
Bifidobacterium bifidum modulation of intestinal barrier and intestinal inflammation.R01DK106072 · NIDDK · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI MA, THOMAS Y · 2016 to 2019
$1.8M
Regulation of Intestinal Tight Junction Barrier and Inflammation by AutophagyR01DK114024 · NIDDK · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI NIGHOT, PRASHANT · 2017 to 2021
$1.8M
Role of the chloride channel ClC-2 in intestinal tight junction barrier recoveryK01DK100562 · NIDDK · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI NIGHOT, PRASHANT · 2014 to 2018
$684k
NIDDK NIH HHS DK100562NIDDK NIH HHS K01 DK100562NIDDK NIH HHS R01 DK106072NIDDK NIH HHS R01 DK114024NIDDK NIH HHS R01 DK121073NIGMS NIH HHS P20 GM121176NIGMS NIH HHS P20-GM-121176
6 · The paper itself

Abstract

BACKGROUND AND

aimsFunctional loss of the gut epithelium's paracellular tight junction [TJ] barrier and defective autophagy are factors potentiating inflammatory bowel disease [IBD]. Previously, we showed the role of autophagy in enhancing the intestinal TJ barrier via pore-forming claudin-2 degradation. How autophagy regulates the TJ barrier-forming proteins remains unknown. Here, we investigated the role of autophagy in the regulation of occludin, a principal TJ component involved in TJ barrier enhancement.

resultsAutophagy induction using pharmacological activators and nutrient starvation increased total occludin levels in intestinal epithelial cells, mouse colonocytes and human colonoids. Autophagy induction enriched membrane occludin levels and reduced paracellular permeability of macromolecules. Autophagy-mediated TJ barrier enhancement was contingent on the presence of occludin as OCLN-/- nullified its TJ barrier-enhancing effect against macromolecular flux. Autophagy inhibited the constitutive degradation of occludin by preventing its caveolar endocytosis from the membrane and protected against inflammation-induced TJ barrier loss. Autophagy enhanced the phosphorylation of ERK-1/2 and inhibition of these kinases in Caco-2 cells and human colonic mucosa prevented the macromolecular barrier-enhancing effects of autophagy. In vivo, autophagy induction by rapamycin enhanced occludin levels in wild-type mouse intestines and protected against lipopolysaccharide- and tumour necrosis factor-α-induced TJ barrier loss. Disruption of autophagy with acute Atg7 knockout in adult mice decreased intestinal occludin levels, increasing baseline colonic TJ permeability and exacerbating the effect of experimental colitis.

conclusionOur data suggest a novel role of autophagy in promoting the intestinal TJ barrier by increasing occludin levels in an ERK1/2 mitogen-activated protein kinase-dependent mechanism.

Indexed as

Intestinal MucosaTight JunctionsAnimalsAutophagyCaco-2 CellsHumansMiceOccludinPermeabilityTight Junction ProteinsOccludinTight Junction ProteinsAutophagyinflammatory bowel diseaseintestinal permeabilityoccludintight junction

Identifiers

PMID36219473
PMCPMC10069622
OpenAlexW4304480691

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.