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Regulation of Tight Junctions’ Functional Integrity

Role of a Urinary Factor, Lipids and Ouabain

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Book cover Tight Junctions

Abstract

The growing molecular complexity of the tight junction (TJ), its ability to modulate the degree of sealing according to physiological requirements, and the fact that its transepithelial electrical resistance (TER) ranges over several orders of magnitude, indicate that there must be a number of agents modulating its permeability. The interest to find these agents stems from an urgency to make the TJ tighter (e.g., to prevent antigen absorption in autoimmune diseases), or to make it leakier (e.g., to allow the absorption of orally administered pharmaceutical drugs). In the present chapter we discuss three forms of modifying the degree of sealing of the TJ: (1) A peptidic factor extracted from urine that makes the TJ tighter, decreases the cellular content of claudin-2, and prompts the relocalization of claudin-4; (2) An experimentally induced modification of the lipidic composition of the plasma membrane that changes some basic attributes of the TJ; and (3) ouabain, a substance that specifically inhibits Na+,K+-ATPase both as an enzyme and as a ion pump, and induces an inotropic activity in heart muscle fibers. Yet we discuss here a newly found property of ouabain: the triggering of a cascade of phosphorylations that results in the opening of the TJ, as part of an overall cell detachment. Interestingly, at concentrations of ouabain within physiological ranges that do not fully detach the cell, the release of the grip induced by this substance sends specific nuclear addressed molecules (NACos) from the diverse sites of attachment to the nucleus, where they modulate the expression of genes that influence proliferation and differentiation.

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Shoshani, L., Flores-BenÍtez, D., Gonzalez-Mariscal, L., Contreras, R.G. (2006). Regulation of Tight Junctions’ Functional Integrity. In: Tight Junctions. Springer, Boston, MA. https://doi.org/10.1007/0-387-36673-3_11

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