Protective role of FKBP51 in calcium entry-induced endothelial barrier disruption


Pulmonary artery endothelial cells (PAECs) express a cation current, ISOC (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 ISOC but not other calcium entry pathways in PAECs. However, it is unknown whether FKBP51-mediated inhibition of ISOC 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 ISOC 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 ISOC 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. . . . .

Read the full article online


Endothelin and Endothelium & Epithelium and Epithelial Transport
Pulmonary Arterial Hypertension
Pulmonary Hypertension


Caleb L. Hamilton, Pierre I. Kadeba, Audrey A. Vasauskas, Viktoriya Solodushko, Anna K. McClinton, Mikhail Alexeyev, Jonathan G. Scammell, Donna L. Cioffi

Published in:

Pulmonary Circulation Vol 8: No 1 cover image

March 2018

Pulmonary Circulation Vol 8: No 1

View this journal

Our research platform is the world.

Through worldwide collaboration, we can begin to answer the question of a global disease.

Join the PVRI