Larazotide Acetate Protects the Intestinal Mucosal Barrier from Anoxia/Reoxygenation Injury via Various Cellular Mechanisms.

Kim J, Madan JP, Laumas S, Krishnan BR, Jin Y

Biomedicines12 Oct 2025Cited by 2 (Europe PMC)

PMID41153766PMCIDPMC12561949DOI10.3390/biomedicines13102483PepBankPUB-41153766

Summary

Background/Objective: Larazotide acetate (LA) is a synthetic octapeptide under development as a therapeutic candidate for celiac disease, acting to reduce intestinal permeability and regulate tight junctions (TJs). Although several studies have shown barrier-protective effects, the cellular mechanisms underlying LA's actions in the intestinal epithelium remain unclear. This study aimed to elucidate the mechanistic roles of LA in maintaining intestinal epithelial integrity during cellular injury. Methods: C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury. Transepithelial electrical resistance (TEER), TJ protein localization, and phosphorylation of myosin light chain-2 (MLC-2) were analyzed. In addition, RNA sequencing was conducted to identify differentially expressed genes and signaling pathways affected by LA treatment. Results: LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury. Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration. LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings. Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions. Conclusions: LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with "leaky gut" and mucosal injury.

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

Results from this study5

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

01LabIn vitro (cells)Mechanism
In injured cell monolayers, larazotide pretreatment significantly increased TEER.
In plain wordsIn cells with anoxia/reoxygenation injury, larazotide increased electrical barrier resistance.
Peptide
Larazotide
Outcome
IncreaseTEER
Study
n: not reported in source
C2BBe1 and leaky IPEC-J2 monolayers with anoxia/reoxygenation injury
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
10 mMAs given in this study.
Source sentences
Summary
LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury.
1 context sentence(design, population, supporting numbers)
Summary · context
C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury.
Show in the study text Report a problemFND-4115376601
02LabIn vitro (cells)Mechanism
In injured cell monolayers, larazotide pretreatment preserved tight junction protein organization.
In plain wordsIn cells with anoxia/reoxygenation injury, larazotide preserved tight junction protein organization.
Peptide
Larazotide
Outcome
Not applicableTight junction protein organization
Study
n: not reported in source
C2BBe1 and leaky IPEC-J2 monolayers with anoxia/reoxygenation injury
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
10 mMAs given in this study.
Source sentences
Summary
LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury.
1 context sentence(design, population, supporting numbers)
Summary · context
C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury.
Show in the study text Report a problemFND-4115376602
03LabIn vitro (cells)Mechanism
In injured cell monolayers, larazotide reduced MLC-2 phosphorylation, likely through ROCK pathway modulation.
In plain wordsIn cells, larazotide reduced MLC-2 phosphorylation, possibly through the ROCK pathway.
Peptide
Larazotide
Outcome
DecreaseMLC-2 phosphorylation
Study
n: not reported in source
C2BBe1 and leaky IPEC-J2 monolayers with anoxia/reoxygenation injury
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
10 mMAs given in this study.
Source sentences
Summary
LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings.
1 context sentence(design, population, supporting numbers)
Summary · context
C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury.
Show in the study text Report a problemFND-4115376604
04LabIn vitro (cells)Mechanism
In cell monolayers, larazotide enhanced cellular proliferation.
In plain wordsIn cells, larazotide increased cell proliferation.
Peptide
Larazotide
Outcome
IncreaseCellular proliferation
Study
n: not reported in source
C2BBe1 and leaky IPEC-J2 monolayers with anoxia/reoxygenation injury
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
10 mMAs given in this study.
Source sentences
Summary
Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions.
1 context sentence(design, population, supporting numbers)
Summary · context
C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury.
Show in the study text Report a problemFND-4115376605
05Computer modelIn silicoMechanism
Larazotide-treated cell monolayers showed enrichment of genes related to barrier regulation, small GTPase signaling, phosphorylation, proliferation and migration.
In plain wordsIn cells, larazotide treatment enriched genes related to barrier regulation, signaling, phosphorylation, proliferation and migration.
Peptide
Larazotide
Outcome
Not applicableTranscriptomic pathway enrichment
Study
n: not reported in source
Transcriptomic gene and pathway enrichment analysis of larazotide-treated cell monolayers
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration.
1 context sentence(design, population, supporting numbers)
Summary · context
C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury.
Show in the study text Report a problemFND-4115376603

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

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