Intestinal permeability and its regulation by zonulin: Diagnostic and therapeutic implications
Open accessAbstract
One of the most important and overlooked functions of the gastrointestinal tract is to provide a dynamic barrier to tightly controlled antigen trafficking through both the transcellular and paracellular pathways. Intercellular tight junctions (TJ) are the key structures regulating paracellular trafficking of macromolecules. Although steady progress has been made in understanding TJ ultrastructure, relatively little is known about their pathophysiological regulation. Our discovery of zonulin, the only known physiological modulator of intercellular TJ described so far, increased understanding of the intricate mechanisms that regulate gut permeability and led us to appreciate that its up-regulation in genetically susceptible individuals may lead to immune-mediated diseases. This information has translational implications, because the zonulin pathway is currently exploited to develop both diagnostic and therapeutic applications pertinent to a variety of immune-mediated diseases.
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Zonulin is the only physiological modulator of tight junctions described to date.
“Zonulin, the only physiological modulator of tight junctions described to date, was discovered as the precursor of haptoglobin-2 (pre-Hp2) [266] and is essential for the regulation of intestinal permeability [267,268,269] (Figure 3).”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [266]
Zonulin was discovered as the precursor of haptoglobin-2 (pre-Hp2).
“Zonulin, the only physiological modulator of tight junctions described to date, was discovered as the precursor of haptoglobin-2 (pre-Hp2) [266] and is essential for the regulation of intestinal permeability [267,268,269] (Figure 3).”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [266]
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- Authors
- Fasano, A.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Fasano, Alessio
- ORCID
- Fasano, Alessio
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 10
- Issue
- 10
- Pages
- 1096-1100
- ISSN
- 1542-3565 (ISSN-L)
- PMC
- PMC3458511
- OpenAlex
- W1988279036
- Cited by
- 402
- References
- 15
- Citations by year
- 2026: 32 · 2025: 37 · 2024: 49 · 2023: 37 · 2022: 50 · 2021: 37 · 2020: 47 · 2019: 36 · 2018: 14 · 2017: 16 · 2016: 21 · 2015: 12 · 2014: 10 · 2013: 3 · 2012: 1
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Gastroenterology and Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 48373, R01DK048373, R21DK078699, DK-078699)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- intestinal permeability, zonulin, tight junctions, paracellular permeability, transcellular permeability, antigen trafficking, immune-mediated diseases, intestinal barrier
- MeSH terms
- Cholera Toxin, Gastrointestinal Diseases, Haptoglobins, Humans, Immune System Diseases, Intestinal Mucosa, Permeability, Protein Precursors, Tight Junctions
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