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Study · In vitro (cells) · mouse · 2018

1 result

Marked differences in tight junction composition and macromolecular permeability among different intestinal cell types.

Pearce SC, Al-Jawadi A, Kishida K, Yu S, Hu M, Fritzky LF, Edelblum KL, Gao N, Ferraris RP

BMC biology1 Feb 2018Cited by 109 (Europe PMC)

PMID29391007 (opens in a new tab)PMCIDPMC5793346 (opens in a new tab)DOI10.1186/s12915-018-0481-z (opens in a new tab)PepBankPUB-29391007
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Summary

BackgroundMammalian small intestinal tight junctions (TJ) link epithelial cells to one another and function as a permselective barrier, strictly modulating the passage of ions and macromolecules through the pore and leak pathways, respectively, thereby preventing the absorption of harmful compounds and microbes while allowing regulated transport of nutrients and electrolytes. Small intestinal epithelial permeability is ascribed primarily to the properties of TJs between adjoining enterocytes (ENTs), because there is almost no information on TJ composition and the paracellular permeability of nonenterocyte cell types that constitute a small but significant fraction of the intestinal epithelia.ResultsHere we directed murine intestinal crypts to form specialized organoids highly enriched in intestinal stem cells (ISCs), absorptive ENTs, secretory goblet cells, or Paneth cells. The morphological and morphometric characteristics of these cells in organoids were similar to those in vivo. The expression of certain TJ proteins varied with cell type: occludin and tricellulin levels were high in both ISCs and Paneth cells, while claudin-1, -2, and -7 expression was greatest in Paneth cells, ISCs, and ENTs, respectively. In contrast, the distribution of claudin-15, zonula occludens 1 (ZO-1), and E-cadherin was relatively homogeneous. E-cadherin and claudin-7 marked mainly the basolateral membrane, while claudin-2, ZO-1, and occludin resided in the apical membrane. Remarkably, organoids enriched in ENTs or goblet cells were over threefold more permeable to 4 and 10 kDa dextran compared to those containing stem and Paneth cells. The TJ-regulator larazotide prevented the approximately tenfold increases in dextran flux induced by the TJ-disrupter AT1002 into organoids of different cell types, indicating that this ZO toxin nonselectively increases permeability. Forced dedifferentiation of mature ENTs results in the reacquisition of ISC-like characteristics in TJ composition and dextran permeability, suggesting that the post-differentiation properties of TJs are not hardwired.ConclusionsDifferentiation of adult intestinal stem cells into mature secretory and absorptive cell types causes marked, but potentially reversible, changes in TJ composition, resulting in enhanced macromolecular permeability of the TJ leak pathway between ENTs and between goblet cells. This work advances our understanding of how cell differentiation affects the paracellular pathway of epithelia.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

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

  1. 01LabIn vitro (cells)Efficacy outcome

    In murine intestinal organoids, larazotide prevented the approximately tenfold dextran-flux increase induced by AT1002.

    In plain wordsIn lab tests, larazotide prevented the approximately tenfold rise in dextran passage caused by AT1002 in mouse intestinal organoids.

    Peptide
    Larazotide
    Outcome
    DecreaseDextran flux
    Study

    mousen: not reported in source

    Intestinal organoids
    Comparator
    AT1002 challenge
    Outcome group
    Gastrointestinal protection · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The TJ-regulator larazotide prevented the approximately tenfold increases in dextran flux induced by the TJ-disrupter AT1002 into organoids of different cell types, indicating that this ZO toxin nonselectively increases permeability.
    1 context sentence
    Summary · context
    Here we directed murine intestinal crypts to form specialized organoids highly enriched in intestinal stem cells (ISCs), absorptive ENTs, secretory goblet cells, or Paneth cells.

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Version history

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  1. Version 2Current

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

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