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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
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5655;
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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