Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions

Intestinal ischemia results in mucosal injury, including paracellular barrier loss due to disruption of tight junctions. Larazotide acetate (LA), a small peptide studied in Phase III clinical trials for treatment of celiac disease, regulates tight junctions (TJs). We hypothesized that LA would dose-...

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Veröffentlicht in:PloS one 2021-04, Vol.16 (4), p.e0250165-e0250165
Hauptverfasser: Slifer, Zachary M, Hernandez, Liliana, Pridgen, Tiffany A, Carlson, Alexandra R, Messenger, Kristen M, Madan, Jay, Krishnan, B Radha, Laumas, Sandeep, Blikslager, Anthony T
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Sprache:eng
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Zusammenfassung:Intestinal ischemia results in mucosal injury, including paracellular barrier loss due to disruption of tight junctions. Larazotide acetate (LA), a small peptide studied in Phase III clinical trials for treatment of celiac disease, regulates tight junctions (TJs). We hypothesized that LA would dose-dependently hasten recovery of intestinal ischemic injury via modulation of TJs. Ischemia-injured tissue from 6-8-week-old pigs was recovered in Ussing chambers for 240-minutes in the presence of LA. LA (1 μM but not 0.1 μM or 10 μM) significantly enhanced transepithelial electrical resistance (TER) above ischemic injured controls and significantly reduced serosal-to-mucosal flux LPS (P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0250165