Paracellular transport: Opening the gates for growth

Claudins are essential components of the intercellular tight junction and major determinants of paracellular solute fluxes across epithelia and endothelia. Many members of this family display a distinct charge or size specificity, whereas others render the epithelium impermeable to transport. Due to intercellular localization, claudin-mediated transport processes are passive and driven by an electrochemical gradient. In epithelial tissues, claudins exhibit a temporal–spatial expression pattern corresponding with regional and local solute transport profiles. Whereas paracellular transport mechanisms in organs such as intestine and kidney have been extensively investigated, little is known about the molecular mechanisms determining solute transport in the peritoneum, and thus the determinants of peritoneal dialysis. Given the ubiquitous expression of claudins in endothelia and epithelia, it is predictable that claudins also contribute to pore formation and determination in the peritoneum, and that they are involved in solute flux. Therefore, we review the basic characteristics of claudin family members and their function as exemplified in renal tubular transport and give an outlook to what extent claudin family members might be of importance for solute reabsorption across the peritoneal membrane.

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Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00043.2009 ◽

2009 ◽

Vol 297 (2) ◽

pp. L219-L227 ◽

Cited By ~ 99

Author(s):

Charlie Wray ◽

Ying Mao ◽

Jue Pan ◽

Anita Chandrasena ◽

Frank Piasta ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Tight Junction ◽

Pulmonary Edema ◽

Barrier Function ◽

Mapk Pathway ◽

Paracellular Transport ◽

Epithelial Barrier ◽

Altered Expression ◽

Alveolar Epithelial

Intact alveolar barrier function is associated with better outcomes in acute lung injury patients; however, the regulation of alveolar epithelial paracellular transport during lung injury has not been extensively investigated. This study was undertaken to determine whether changes in tight junction claudin expression affect alveolar epithelial barrier properties and to determine the mechanisms of altered expression. In anesthetized mice exposed to ventilator-induced lung injury, claudin-4 was specifically induced among tight junction structural proteins. Real-time PCR showed an eightfold increase in claudin-4 expression in the lung injury model. To examine the role of this protein in barrier regulation, claudin-4 function was inhibited with small interfering RNA (siRNA) and a blocking peptide derived from the binding domain of Clostridium perfringens enterotoxin (CPEBD). Inhibition of claudin-4 decreased transepithelial electrical resistance but did not alter macromolecule permeability in primary rat and human epithelial cells. In mice, CPEBD decreased air space fluid clearance >33% and resulted in pulmonary edema during moderate tidal volume ventilation that did not induce edema in control peptide-treated mice. In vitro phorbol ester induced a ninefold increase in claudin-4 expression that was dependent on PKC activation and the JNK MAPK pathway. These data establish that changes in alveolar epithelial claudin expression influence paracellular transport, alveolar fluid clearance rates, and susceptibility to pulmonary edema. We hypothesize that increased claudin-4 expression early in acute lung injury represents a mechanism to limit pulmonary edema and that the regulation of alveolar epithelial claudin expression may be a novel target for acute lung injury therapy.

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Paracellular transport to the coral calcifying medium: effects of environmental parameters

Journal of Experimental Biology ◽

10.1242/jeb.227074 ◽

2020 ◽

Vol 223 (17) ◽

pp. jeb227074 ◽

Cited By ~ 4

Author(s):

Alexander A. Venn ◽

Coralie Bernardet ◽

Apolline Chabenat ◽

Eric Tambutté ◽

Sylvie Tambutté

Keyword(s):

Environmental Parameters ◽

Intercellular Junctions ◽

Paracellular Permeability ◽

Paracellular Transport ◽

Medium Effects ◽

Stylophora Pistillata ◽

Seawater Acidification ◽

Imaging Approach ◽

Transport Of Ions

ABSTRACTCoral calcification relies on the transport of ions and molecules to the extracellular calcifying medium (ECM). Little is known about paracellular transport (via intercellular junctions) in corals and other marine calcifiers. Here, we investigated whether the permeability of the paracellular pathway varied in different environmental conditions in the coral Stylophora pistillata. Using the fluorescent dye calcein, we characterised the dynamics of calcein influx from seawater to the ECM and showed that increases in paracellular permeability (leakiness) induced by hyperosmotic treatment could be detected by changes in calcein influx rates. We then used the calcein-imaging approach to investigate the effects of two environmental stressors on paracellular permeability: seawater acidification and temperature change. Under conditions of seawater acidification (pH 7.2) known to depress pH in the ECM and the calcifying cells of S. pistillata, we observed a decrease in half-times of calcein influx, indicating increased paracellular permeability. By contrast, high temperature (31°C) had no effect, whereas low temperature (20°C) caused decreases in paracellular permeability. Overall, our study establishes an approach to conduct further in vivo investigation of paracellular transport and suggests that changes in paracellular permeability could form an uncharacterised aspect of the physiological response of S. pistillata to seawater acidification.

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