Cited by 93Inflammatory Bowel DiseaseProtease and Inhibitor MechanismsBarrier Structure and Function Studies

Matrix Metalloproteinase-9 (MMP-9) induced disruption of intestinal epithelial tight junction barrier is mediated by NF-κB activation

Open access
Al-Sadi, Rana, Engers, Jessica, Haque, Mohammad, King, Steven, Al-Omari, Deemah, Ma, Thomas Y.·2021·PLOS ONE

Abstract

Background: Matrix Metalloproteinase-9 (MMP-9) has been shown to play a key role in mediating inflammation and tissue damage in inflammatory bowel disease (IBD). In patients with IBD, the intestinal tight junction (TJ) barrier is compromised as characterized by an increase in intestinal permeability. MMP-9 is elevated in intestinal tissue, serum and stool of patients with IBD. Previous studies from our laboratory showed that MMP-9 causes an increase in intestinal epithelial TJ permeability and that the MMP-9 induced increase in intestinal permeability is an important pathogenic factor contributing to the development of intestinal inflammation in IBD. However, the intracellular mechanisms that mediate the MMP-9 modulation of intestinal barrier function remain unclear. Aims: The main aim of this study was to further elucidate the molecular mechanisms involved in MMP-9 induced increase in intestinal epithelial TJ permeability using Caco-2 monolayers as an in-vitro model system. Results: MMP-9 induced increase in Caco-2 TJ permeability was associated with activation and cytoplasmic-to-nuclear translocation of NF-κB p65. Knocking-down NF-κB p65 by siRNA transfection prevented the MMP-9 induced expression of the NF-κB target gene IL-8, myosin light chain kinase (MLCK) protein expression, and subsequently prevented the increase in Caco-2 TJ permeability. In addition, the effect of MMP-9 on Caco-2 intestinal epithelial TJ barrier function was not mediated by apoptosis or necrosis. Conclusion: Our data show that the MMP-9 induced disruption of Caco-2 intestinal epithelial TJ barrier function is regulated by NF-κB pathway activation of MLCK.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0249544

Cites

94 of 94 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The complex signaling pathway at the blood/CNS interface is constituted by the sequence of selectins, chemokines and integrins, resulting in emperipolesis through matrix metalloproteinases type 9 (MMP9) activation and tight-junctions disruption.

    “Thus, the complex signaling pathway is constituted by the sequence of selectins, chemokines and integrins at the interface blood/CNS, resulting in emperipolesis through matrix metalloproteinases type 9 (MMP9) activation and tight-junctions disruption [74,75].”

    From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [75]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 95 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [91]Nighot P, Al-Sadi R, Rawat M, Guo S, Watterson DM, Ma T. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis. Am J Physiol Gastrointest Liver Physiol. 309(12): G988– 97. Epub 2015/10/31. doi: ajpgi.00256.2015 [pii] 10.1152/ajpgi.00256.2015 26514773 PMC4683300 · DOI

Cited by

Sorted by citations

Authors
Al-Sadi, R., Engers, J., Haque, M., King, S., Al-Omari, D., & Ma, T. Y.
Affiliations
  • Pennsylvania State University (US)
  • University of New Mexico (US)
Corresponding author
  • Engers, Jessica
  • Haque, Mohammad
  • King, Steven
  • Al-Omari, Deemah
  • Ma, Thomas Y.
Venue
PLOS ONE
Published
2021-04-07
Volume
16
Issue
4
Pages
e0249544
ISSN
1932-6203 (ISSN-L)
OpenAlex
W3144084593
Cited by
93
References
95
Citations by year
2026: 17 · 2025: 23 · 2024: 22 · 2023: 14 · 2022: 13 · 2021: 3
FWCI
7.35
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Crohn's and Colitis Foundation of America (326502)
  • Penn State College of Medicine
  • National Institute of Diabetes and Digestive and Kidney Diseases (R0-1-DK-106072-01, R01-DK-121073-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
MMP-9, NF-κB p65, intestinal permeability, inflammatory bowel disease, myosin light chain kinase, interleukin-8, Caco-2 cells, NF-κB nuclear translocation, intestinal epithelial barrier dysfunction
MeSH terms
Cell Membrane Permeability, Gene Expression Regulation, Humans, Intestinal Mucosa, Models, Biological, Myosin-Light-Chain Kinase, Inflammatory Bowel Diseases, Interleukin-8, NF-kappa B, Caco-2 Cells, Tight Junctions, Matrix Metalloproteinase 9

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review