Calcium flux and endothelial dysfunction during acute lung injury: a STIMulating target for therapy
Eric J. Seeley, … , Paul Rosenberg, Michael A. Matthay
Eric J. Seeley, … , Paul Rosenberg, Michael A. Matthay
Published February 22, 2013
Citation Information: J Clin Invest. 2013;123(3):1015-1018. https://doi.org/10.1172/JCI68093.
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Commentary

Calcium flux and endothelial dysfunction during acute lung injury: a STIMulating target for therapy

Abstract

Bacterial pathogen-associated molecular pattern molecules (PAMPs) such as LPS activate the endothelium and can lead to lung injury, but the signaling pathways mediating endothelial injury remain incompletely understood. In a recent issue of the JCI, Gandhirajan et al. identify STIM1, an ER calcium sensor, as a key link between LPS-induced ROS, calcium oscillations, and endothelial cell (EC) dysfunction. In addition, they report that BTP2, an inhibitor of calcium channels, attenuates lung injury. This study identifies a novel endothelial signaling pathway that could be a future target for the treatment of lung injury.

Authors

Eric J. Seeley, Paul Rosenberg, Michael A. Matthay

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Figure 1

STIM1-mediated calcium oscillations connect TLR4 signals and endothelial dysfunction during lung injury.

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STIM1-mediated calcium oscillations connect TLR4 signals and endothelial...
(A) The normal pulmonary endothelium maintains a tight barrier between endothelial cells, the interstitium, and the alveolar space. This preserves alveolar gas exchange. (B) LPS-stimulated endothelial activation leads to ROS accumulation, calcium oscillations, and NFAT-mediated loss of barrier function. This allows leakage of protein-rich edema fluid into the alveolus, causing impaired gas exchange and hypoxemia. (C) BTP2 therapy inhibits calcium flux through Orai1 channels, dissociates ROS from NFAT nuclear translocation, inhibits subsequent endothelial injury and apoptosis.