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Claudin-2: Roles beyond Permeability Functions

Keenan Research Centre for Biomedical Science of the St. Michael’s Hospital and Department of Surgery, University of Toronto, Toronto, ON M5B 1W8, Canada
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Int. J. Mol. Sci. 2019, 20(22), 5655; https://doi.org/10.3390/ijms20225655
Received: 13 October 2019 / Revised: 8 November 2019 / Accepted: 9 November 2019 / Published: 12 November 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Claudin-2 is expressed in the tight junctions of leaky epithelia, where it forms cation-selective and water permeable paracellular channels. Its abundance is under fine control by a complex signaling network that affects both its synthesis and turnover in response to various environmental inputs. Claudin-2 expression is dysregulated in many pathologies including cancer, inflammation, and fibrosis. Claudin-2 has a key role in energy-efficient ion and water transport in the proximal tubules of the kidneys and in the gut. Importantly, strong evidence now also supports a role for this protein as a modulator of vital cellular events relevant to diseases. Signaling pathways that are overactivated in diseases can alter claudin-2 expression, and a good correlation exists between disease stage and claudin-2 abundance. Further, loss- and gain-of-function studies showed that primary changes in claudin-2 expression impact vital cellular processes such as proliferation, migration, and cell fate determination. These effects appear to be mediated by alterations in key signaling pathways. The specific mechanisms linking claudin-2 to these changes remain poorly understood, but adapters binding to the intracellular portion of claudin-2 may play a key role. Thus, dysregulation of claudin-2 may contribute to the generation, maintenance, and/or progression of diseases through both permeability-dependent and -independent mechanisms. The aim of this review is to provide an overview of the properties, regulation, and functions of claudin-2, with a special emphasis on its signal-modulating effects and possible role in diseases. View Full-Text
Keywords: claudin-2; tight junctions; epithelium; cancer; inflammation; fibrosis; paracellular permeability; proliferation; migration claudin-2; tight junctions; epithelium; cancer; inflammation; fibrosis; paracellular permeability; proliferation; migration
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Venugopal, S.; Anwer, S.; Szászi, K. Claudin-2: Roles beyond Permeability Functions. Int. J. Mol. Sci. 2019, 20, 5655.

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