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Regulation of adherens junctions and epithelial paracellular permeability: a novel function for polyamines
Abstract
Maintenance of intestinal mucosal epithelial integrity requires polyamines that are involved in the multiple signaling pathways controlling gene expression and different epithelial cell functions. Integrity of the intestinal epithelial barrier depends on a complex of proteins composing different intercellular junctions, including tight junctions, adherens junctions, and desmosomes. E-cadherin is primarily found at the adherens junctions and plays a critical role in cell-cell adhesions that are fundamental to formation of the intestinal epithelial barrier. The current study determined whether polyamines regulate intestinal epithelial barrier function by altering E-cadherin expression. Depletion of cellular polyamines by alpha-difluoromethylornithine (DFMO) reduced intracellular free Ca2+ concentration ([Ca2+]cyt), decreased E-cadherin expression, and increased paracellular permeability in normal intestinal epithelial cells (IEC-6 line). Polyamine depletion did not alter expression of tight junction proteins such as zona occludens (ZO)-1, ZO-2, and junctional adhesion molecule (JAM)-1. Addition of exogenous polyamine spermidine reversed the effects of DFMO on [Ca2+]cyt and E-cadherin expression and restored paracellular permeability to near normal. Elevation of [Ca2+]cyt by the Ca2+ ionophore ionomycin increased E-cadherin expression in polyamine-deficient cells. In contrast, reduction of [Ca2+]cyt by polyamine depletion or removal of extracellular Ca2+ not only inhibited expression of E-cadherin mRNA but also decreased the half-life of E-cadherin protein. These results indicate that polyamines regulate intestinal epithelial paracellular barrier function by altering E-cadherin expression and that polyamines are essential for E-cadherin expression at least partially through [Ca2+]cyt.
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“It was shown that depletion of cellular polyamines by α-difluoromethylornithine reduced intracellular free Ca2+ concentrations in normal IECs (IEC-6 cell line),127 which leads to decreased expression of E-cadherin and increased paracellular permeability.”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [127]
In the citing paper
“These studies suggested that polyamines regulate gut barrier function through upregulating E-cadherin in an intracellular Ca2+-dependent manner.127”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [127]
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Metadata
- Authors
- Guo, X., Rao, J. N., Liu, L., Zou, T.-T., Turner, D. J., Bass, B. L., & Wang, J.-Y.
- Affiliations
- University of Maryland, Baltimore (US)
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2003-11
- Volume
- 285
- Issue
- 5
- Pages
- C1174-C1187
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2109680774
- Cited by
- 153
- References
- 66
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 2 · 2017: 6 · 2016: 11 · 2015: 9 · 2014: 9 · 2013: 6 · 2012: 9
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061972, (DK-57819, DK-61972, R01DK057819)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- polyamines, adherens junctions, paracellular permeability, intestinal epithelial barrier, E-cadherin, intracellular calcium, difluoromethylornithine, spermidine, tight junctions, protein stability, IEC-6 cells
- MeSH terms
- Animals, Calcium, Cell Line, Cell Membrane Permeability, Epithelial Cells, Intestinal Mucosa, Polyamines, Cadherins, Adherens Junctions, Rats
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