Ducza Eszter, Csányi Adrienn, Szőke Éva, Pohóczky Krisztina, Hajagos-Tóth Judit, Kothencz Anna, Tiszai Zita, Gáspár Róbert
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Hungary.
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.
Heliyon. 2019 Oct 22;5(10):e02697. doi: 10.1016/j.heliyon.2019.e02697. eCollection 2019 Oct.
Aquaporins (AQPs) are channel proteins that facilitate the rapid passive movement of water. In our studies it was proved that the decreased AQP5 expression is followed by the increase of uterine contractility. The transient receptor potential vanilloid 4 (TRPV4) is a calcium channel, which is activated in response to osmotic changes. Our aim was to determine the possible role of AQP5 in this osmotic regulation of TRPV4, thus in pregnant uterine contraction.
We used RT-PCR and Western blot techniques for the detection of the TRPV4 expression during pregnancy in rat uterus. The localization of AQP5 and TRPV4 was determined by immunohistochemical studies. The role of TRPV4 in uterus contraction was investigated in an isolated organ bath system. uterus contractions were stimulated with KCl and its effect was investigated with the selective TRPV4 agonist (RN1747) and antagonist (RN1734).
The TRPV4 expression continuously increased from day 18 to the last day of pregnancy. The co-expression of TRPV4 and AQP5 in the myometrium and endometrium was determined in the late pregnant uterus. The TRPV4 antagonist and agonist significantly decreased and increased uterine contraction, respectively, especially on the last day of pregnancy.
We presume the decreased AQP5 expression triggers hypertonic stress, which activates TRPV4 and increases uterus contraction on the day of labor. Based on these findings, we suppose the TRPV4 effect on uterus contraction is AQP5 control, which could be a new target in preterm birth therapy.
水通道蛋白（AQPs）是促进水快速被动转运的通道蛋白。我们的研究证明，AQP5表达降低后子宫收缩性增加。瞬时受体电位香草酸受体4（TRPV4）是一种钙通道，可响应渗透压变化而被激活。我们的目的是确定AQP5在TRPV4这种渗透压调节中以及在妊娠子宫收缩中可能发挥的作用。
我们使用逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹技术检测大鼠子宫妊娠期间TRPV4的表达。通过免疫组织化学研究确定AQP5和TRPV4的定位。在离体器官浴系统中研究TRPV4在子宫收缩中的作用。用氯化钾刺激子宫收缩，并使用选择性TRPV4激动剂（RN1747）和拮抗剂（RN1734）研究其作用效果。
从妊娠第18天到妊娠最后一天，TRPV4表达持续增加。在妊娠晚期子宫中确定了TRPV4和AQP5在子宫肌层和子宫内膜中的共表达。TRPV4拮抗剂和激动剂分别显著降低和增加子宫收缩，尤其是在妊娠最后一天。
我们推测AQP5表达降低引发高渗应激，激活TRPV4并在分娩日增加子宫收缩。基于这些发现，我们认为TRPV4对子宫收缩的影响受AQP5调控，这可能是早产治疗的一个新靶点。
