Characterizing zonulin and par2 Expression in Zonulin Transgenic and Zonulin Inhibition Mouse Models of Motility and Inflammation.

Martinez EE, Philpott JD, Lan J, Rodriguez Hovnanian KM, Fasano A

International journal of molecular sciences2 Jul 2025Cited by 1 (Europe PMC)

PMID40650159PMCIDPMC12249515DOI10.3390/ijms26136381PepBankPUB-40650159

Summary

We aimed to examine the effect of zonulin and zonulin inhibition on gastrointestinal (GI) motility and the mRNA expression of zonulin and the protease-activated receptor 2 (par2), the primary receptor for zonulin, under conditions of inflammation by lipopolysaccharide (LPS) injection. The experimental models included zonulin transgenic mice (ztm), par2 knockout ztm (ztm-par2 -/-), ztm exposed to the zonulin inhibitor AT1001 (ztm-AT1001), and wildtype mouse controls. GI transit was measured by fluorescein isothiocyanate-dextran and mRNA expression by real-time quantitative polymerase chain reaction in whole, and in epithelial and non-epithelial tissues of all GI segments. There were no differences in the GI transit between mouse groups at baseline. After the LPS injection, ztm mice had an attenuated slowing of the GI transit compared to wildtype mice. The zonulin-inhibited mice had motility patterns similar to wildtype mice. zonulin upregulation was noted in GI segments of the ztm, ztm-par2 -/-, and ztm-AT1001 after the LPS injection. Differences in motility patterns between ztm and zonulin inhibition models despite zonulin expression in GI segments of all mouse groups supports that PAR2 is key for zonulin's effect on motility under conditions of inflammation. However, the findings from the epithelial and non-epithelial compartments suggest that the pathway of activity is complex and likely indirect.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

1 result from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Activity measurement
In zonulin-inhibited mice exposed to AT1001, motility patterns were similar to wildtype mice.
In plain wordsIn mice, gut movement patterns with AT1001 were similar to those in wildtype mice.
Peptide
Larazotide
Outcome
No significant changeMotility patterns after LPS
Study
mousen: not reported in source
zonulin transgenic mice exposed to AT1001
Comparator
wildtype mice
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
The zonulin-inhibited mice had motility patterns similar to wildtype mice.
1 context sentence(design, population, supporting numbers)
Summary · context
The experimental models included zonulin transgenic mice (ztm), par2 knockout ztm (ztm-par2 -/-), ztm exposed to the zonulin inhibitor AT1001 (ztm-AT1001), and wildtype mouse controls.
Show in the study text Report a problemFND-4065015902

Studies that did not test the peptide alone2

In this study, Larazotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Larazotide.

02AnimalNot a test of Larazotide aloneAnimal study (in vivo)Activity measurement
In mice, baseline gastrointestinal transit did not differ among groups, including the AT1001 group.
In plain wordsIn mice, baseline gut transit did not differ among groups, including mice exposed to AT1001.
Peptide
Larazotide
Outcome
No significant changeBaseline gastrointestinal transit
Study
mousen: not reported in source
zonulin transgenic mice exposed to AT1001
Comparator
other mouse groups
Outcome group
Gastrointestinal protection · Gastrointestinal
Source sentences
Summary
There were no differences in the GI transit between mouse groups at baseline.
1 context sentence(design, population, supporting numbers)
Summary · context
The experimental models included zonulin transgenic mice (ztm), par2 knockout ztm (ztm-par2 -/-), ztm exposed to the zonulin inhibitor AT1001 (ztm-AT1001), and wildtype mouse controls.
In this study, Larazotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Larazotide.
Show in the study text Report a problemFND-4065015901
03AnimalNot a test of Larazotide aloneAnimal study (in vivo)Mechanism
In AT1001-exposed zonulin transgenic mice, zonulin expression increased after LPS, as in the other named transgenic groups.
In plain wordsIn mice exposed to AT1001, LPS increased zonulin expression, as in the other named transgenic groups.
Peptide
Larazotide
Outcome
IncreaseZonulin expression after LPS
Study
mousen: not reported in source
zonulin transgenic mice exposed to AT1001
Outcome group
Receptor activity and mechanism · Gastrointestinal
Source sentences
Summary
zonulin upregulation was noted in GI segments of the ztm, ztm-par2 -/-, and ztm-AT1001 after the LPS injection.
1 context sentence(design, population, supporting numbers)
Summary · context
The experimental models included zonulin transgenic mice (ztm), par2 knockout ztm (ztm-par2 -/-), ztm exposed to the zonulin inhibitor AT1001 (ztm-AT1001), and wildtype mouse controls.
In this study, Larazotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Larazotide.
Show in the study text Report a problemFND-4065015903

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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