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- W2776142021 abstract "Pulmonary artery endothelial cells (PAECs) express a cation current, I SOC (store‐operated calcium entry current), which when activated permits calcium entry leading to inter‐endothelial cell gap formation. The large molecular weight immunophilin FKBP51 inhibits I SOC but not other calcium entry pathways in PAECs. However, it is unknown whether FKBP51‐mediated inhibition of I SOC is sufficient to protect the endothelial barrier from calcium entry‐induced disruption. The major objective of this study was to determine whether FKBP51‐mediated inhibition of I SOC leads to decreased calcium entry‐induced inter‐endothelial gap formation and thus preservation of the endothelial barrier. Here, we measured the effects of thapsigargin‐induced I SOC on the endothelial barrier in control and FKBP51 overexpressing PAECs. FKBP51 overexpression decreased actin stress fiber and inter‐endothelial cell gap formation in addition to attenuating the decrease in resistance observed with control cells using electric cell‐substrate impedance sensing. Finally, the thapsigargin‐induced increase in dextran flux was abolished in FKBP51 overexpressing PAECs. We then measured endothelial permeability in perfused lungs of FKBP51 knockout (FKBP51 –/– ) mice and observed increased calcium entry‐induced permeability compared to wild‐type mice. To begin to dissect the mechanism underlying the FKBP51‐mediated inhibition of I SOC , a second goal of this study was to determine the role of the microtubule network. We observed that FKBP51 overexpressing PAECs exhibited increased microtubule polymerization that is critical for inhibition of I SOC by FKBP51. Overall, we have identified FKBP51 as a novel regulator of endothelial barrier integrity, and these findings are significant as they reveal a protective mechanism for endothelium against calcium entry‐induced disruption." @default.
- W2776142021 created "2018-01-05" @default.
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- W2776142021 date "2018-01-01" @default.
- W2776142021 modified "2023-09-25" @default.
- W2776142021 title "Protective role of FKBP51 in calcium entry‐induced endothelial barrier disruption" @default.
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- W2776142021 doi "https://doi.org/10.1177/2045893217749987" @default.
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