Evidence map›Paper›PMID 30892937›Full record

ArticleAmerican journal of physiology. Cell physiology2019

Intestinal epithelial tight junction barrier regulation by autophagy-related protein ATG6/beclin 1.

Morgan Wong, Ashwinkumar Subramenium Ganapathy, Eric Suchanec, Laura Laidler, Thomas Ma, Prashant Nighot

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

43 citing papers in PubMed, 62 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

6 authors at 2 institutions in 1 country.

Morgan WongDepartment of Internal Medicine, University of New Mexico School of Medicine , Albuquerque, New Mexico.
Ashwinkumar Subramenium GanapathyDepartment of Medicine, College of Medicine, Pennsylvania State University , Hershey, Pennsylvania.
Eric SuchanecDepartment of Medicine, College of Medicine, Pennsylvania State University , Hershey, Pennsylvania.
Laura LaidlerDepartment of Internal Medicine, University of New Mexico School of Medicine , Albuquerque, New Mexico.
Thomas MaDepartment of Medicine, College of Medicine, Pennsylvania State University , Hershey, Pennsylvania.
Prashant NighotDepartment of Medicine, College of Medicine, Pennsylvania State University , Hershey, Pennsylvania.ORCID 0000-0003-2368-7290
Pennsylvania State University · USUniversity of New Mexico · US

Funding

Unfolded Protein Response and Autophagy in T Helper Cell Effector FunctionP20GM121176 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Monica Rosas Lemus · 2017 to 2026
$24.9M
TNF-alpha Regulation of Intestinal Paracellular TransportR01DK064165 · NIDDK · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI MA, THOMAS Y · 2003 to 2018
$5.2M
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 K01 DK100562NIDDK NIH HHS R01 DK064165NIDDK NIH HHS R01 DK114024NIGMS NIH HHS P20 GM121176
6 · The paper itself

Abstract

A defective tight junction (TJ) barrier is a key pathogenic factor for inflammatory bowel disease. Previously, we have shown that autophagy, a cell survival mechanism, enhances intestinal epithelial TJ barrier function. Autophagy-related protein-6 (ATG6/beclin 1), a key protein in the autophagy pathway, also plays a role in the endocytic pathway. The constitutive role of beclin 1 in the intestinal TJ barrier is not known. In Caco-2 cells, beclin 1 was found to be coimmunoprecipitated with the TJ protein occludin and colocalized with occludin on the membrane. Treatment of Caco-2 cells with beclin 1 peptide [transactivating regulatory protein (Tat)-beclin 1] reduced TJ barrier function. Activation of beclin 1 increased occludin endocytosis and reduced total occludin protein level. In contrast, beclin 1 siRNA transfection enhanced Caco-2 TJ barrier function. In pharmacologic and genetic autophagy inhibition studies, the constitutive function of beclin 1 in the TJ barrier was found to be autophagy independent. However, de novo induction of autophagy with starvation or rapamycin prevented Tat-beclin 1-induced increase in TJ permeability and reduction in occludin level. Induction of autophagy also resulted in reduced beclin 1-occludin association. In mouse colon, beclin 1 colocalized with occludin on the epithelial membrane. Perfusion of mouse colon with beclin 1 peptide caused an increase in colonic TJ permeability that was prevented by in vivo induction of autophagy. These findings show that beclin 1 plays a constitutive, autophagy-independent role in the regulation of intestinal TJ barrier function via endocytosis of occludin. Autophagy terminates constitutive beclin 1 function in the TJ barrier and enhances the TJ barrier.

Indexed as

AnimalsAutophagyBeclin-1Caco-2 CellsFemaleHumansIntestinal MucosaMaleMiceMice, Inbred C57BLTight JunctionsBeclin-1BECN1 protein, humanautophagybeclin 1occludintight junction

Identifiers

PMID30892937
PMCPMC6580157
OpenAlexW2924549428

What Socratic 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 Socratic graph.