Hanna H Allerkamp, Alexander I Bondarenko, Ines Tawfik, Nilüfer Kamali-Simsek, Monika Horvat Mercnik, Corina T Madreiter-Sokolowski, Christian Wadsack
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引用次数: 0
Abstract
Mechanosensation is essential for endothelial cell (EC) function, which is compromised in early-onset preeclampsia (EPE), impacting offspring health. The ion channels Piezo-type mechanosensitive ion channel component 1 (Piezo1) and Transient receptor potential cation channel subfamily V member 4 (TRPV4) are co-regulated mechanosensors in ECs. Current evidence suggests that both channels could mediate aberrant placental endothelial function in EPE. Using isolated feto-placental ECs (fpECs) from early control (EC) and EPE pregnancies, we show functional co-expression of both channels and that Ca2+ influx and membrane depolarization in response to chemical channel activation is reduced in EPE fpECs. Downstream of channel activation, Piezo1 alone can induce phosphorylation of endothelial nitric oxide synthase (eNOS) in fpECs, while combined activation of Piezo1 and TRPV4 only affects eNOS phosphorylation in EPE fpECs. Additionally, combined activation reduces the barrier integrity of fpECs, also with a stronger effect on EPE fpECs. This implies altered Piezo1-TRPV4 co-regulation in EPE. Mechanistically, we suggest this to be driven by changes in the arachidonic acid metabolism in EPE fpECs as identified by RNA-Seq. Targeting of Piezo1 and TRPV4 might hold potential for EPE treatment options in the future.
期刊介绍:
The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.