Curcumin prophylaxis refurbishes alveolar epithelial barrier integrity and alveolar fluid clearance under hypoxia

2020 ◽  
Vol 274 ◽  
pp. 103336 ◽  
Author(s):  
Titto M ◽  
Ankit T ◽  
Saumya B ◽  
Gausal AK ◽  
Sarada SKS
Author(s):  
Vitalii Kryvenko ◽  
István Vadász

A significant number of patients with coronavirus disease 2019 (COVID‑19) develop acute respiratory distress syndrome (ARDS) that is associated with a poor outcome. The molecular mechanisms driving failure of the alveolar barrier upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) infection remain incompletely understood. The Na,K‑ATPase is an adhesion molecule and a plasma membrane transporter that is critically required for proper alveolar epithelial function by both promoting barrier integrity and resolution of excess alveolar fluid, thus enabling appropriate gas exchange. However, numerous SARS-CoV‑2-mediated and COVID‑19-related signals directly or indirectly impair the function of the Na,K-ATPase, thereby potentially contributing to disease progression. In this Perspective, we highlight some of the putative mechanisms of SARS-CoV-2-driven dysfunction of the Na,K‑ATPase, focusing on expression, maturation and trafficking of the transporter. A therapeutic mean to selectively inhibit the maladaptive signals that impair the Na,K-ATPase upon SARS-CoV‑2 infection might be effective in reestablishing the alveolar epithelial barrier and promoting alveolar fluid clearance (AFC) and thus advantageous in patients with COVID‑19-associated ARDS.


2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Holly Sucharski ◽  
Nathan Putz ◽  
Ciara Shaver ◽  
Lorraine Ware ◽  
Julie Bastarache

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Franco Conforti ◽  
Robert Ridley ◽  
Christopher Brereton ◽  
Aiman Alzetani ◽  
Benjamin Johnson ◽  
...  

2009 ◽  
Vol 297 (2) ◽  
pp. L219-L227 ◽  
Author(s):  
Charlie Wray ◽  
Ying Mao ◽  
Jue Pan ◽  
Anita Chandrasena ◽  
Frank Piasta ◽  
...  

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.


2017 ◽  
Vol 139 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Paulina Wawrzyniak ◽  
Marcin Wawrzyniak ◽  
Kerstin Wanke ◽  
Milena Sokolowska ◽  
Kreso Bendelja ◽  
...  

2011 ◽  
Vol 121 (2) ◽  
pp. 346-351 ◽  
Author(s):  
Bernard Rousseau ◽  
Atsushi Suehiro ◽  
Nicholas Echemendia ◽  
Mahalakshmi Sivasankar

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