Significance of transient receptor potential vanilloid 4 and aquaporin 5 co-expression in the rat uterus at term

Abstract

AimsAquaporins (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.Main methodsWe 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. In vitro uterus contractions were stimulated with KCl and its effect was investigated with the selective TRPV4 agonist (RN1747) and antagonist (RN1734).Key findingsThe 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.SignificanceWe 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.

Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers

“…Endometrial cancer arises from tissue lining the uterus (the endometrium) and accounts for about 95% of uterine cancers. Protein and RNA for AQPs 1, 2, 3, 5, 7 and 9 are normally expressed in endometrium, in which the AQPs are thought to be involved in fluid exchange and estrogen-mediated regulatory effects [ 200 , 201 , 202 , 203 , 204 , 205 , 206 ]. AQP1 expression in endometrial cancer has been correlated with histologic grade, extent of myometrial invasion and the likelihood of extrauterine metastasis [ 207 ], but the functional role of AQP1 in this tissue remains to be defined.…”

Uterine contractions in rodent models and humans

“…Whereas LTCCs and TTCCs are activated by the less negative membrane potential at the end of pregnancy, TRPV4 is activated by stretch or heat 74 . TRPV4 expression and activity increases throughout gestation in rats, and TRPV4 expression is higher in myometrium from pregnant women than in myometrium from non‐pregnant women 75,76 . Silencing TRPV4 expression in human myometrial cells prevents them from contracting in a collagen gel matrix 75 .…”

“…74 TRPV4 expression and activity increases throughout gestation in rats, and TRPV4 expression is higher in myometrium from pregnant women than in myometrium from non-pregnant women. 75,76 Silencing TRPV4 expression in human myometrial cells prevents them from contracting in a collagen gel matrix. 75 Similarly, a TRPV4 antagonist attenuates contractions in both rat and mouse myometrium.…”

(Endo)Cannabinoids and Gynaecological Cancers

“…Although the cannabinoid receptors were originally identified in the central nervous system (CNS for type 1 cannabinoid receptor—CB 1 ), where they regulate the psychotropic effect of THC [ 14 ], and the spleen (type 2 cannabinoid receptor—CB 2 ), where they have immunomodulatory functions [ 15 ], it is now clear that they are found throughout the human body [ 16 , 17 ]. The eCBs as ligands not only bind to CB 1 and CB 2 , but also bind to and activate or inhibit the actions of the orphan G-protein-coupled receptors GPR55 [ 18 ] and GPR119 [ 19 ]; moreover, intracellularly, they bind to and activate the transient receptor potential (TRP) channels TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8 [ 20 ], widely expressed in female reproductive tissues [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ], and the nuclear peroxisome proliferator-activated receptor (PPAR) isotypes α, γ, and δ [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], through which they alter gene transcription [ 39 ].…”