Aim of the Study Nuclear factor of activated T-cell (NFATc2), a Ca2+/
calcineurin-dependent
transcription factor, is reported to be activated in human and animal
pulmonary hypertension (PH). KV1.5, a voltage-gated K+ (KV) channel, is expressed in pulmonary artery smooth muscle cells (PASMC) and downregulated in PASMC in patients and animals with PH. Furthermore, activation of NFATc2 downregulates expression of KV1.5 channels, leading to excessive PASMC proliferation. The aim of this study was to investigate the pulmonary vascular expression of NFATc2 and KV1.5 in rats with
nitrofen-induced
congenital diaphragmatic hernia (CDH). Materials and Methods After ethical approval, time-pregnant Sprague-Dawley rats received
nitrofen or vehicle on gestational day 9 (D9). When sacrificed on D21, the fetuses (n = 22) were divided into CDH and control groups. Using quantitative real-time polymerase chain reaction and western blotting, we determined the gene and
protein expression of NFATc2 and KV1.5. Confocal microscopy was used to detect both
proteins in the pulmonary vasculature. Results Relative
mRNA levels of NFATc2 were significantly upregulated and KV1.5 levels were significantly downregulated in CDH lungs compared with controls (p < 0.05). Western blotting confirmed the imbalanced pulmonary
protein expression of both
proteins. An increased pulmonary vascular expression of NFATc2 and a diminished expression of KV1.5 in CDH lungs compared with controls were seen in confocal microscopy. Conclusions This study demonstrates for the first time an altered gene and
protein expression of NFATc2 and KV1.5 in the pulmonary vasculature of
nitrofen-induced CDH. Upregulation of NFATc2 with concomitant downregulation of KV1.5 channels may contribute to abnormal
vascular remodeling resulting in PH in this model.