The progesterone receptor regulates the expression of TRPV4 channel

Abstract

The transient receptor potential cationic channel TRPV4 contributes to different aspects of cell physiology via the generation of a Ca2+ signal and/or depolarization of the membrane potential. TRPV4 channel integrates distinct physical and chemical stimuli, including osmotic and mechanical stress, heat, acidic pH, endogenous ligands, and synthetic agonists such as 4alpha-phorbol 12,13-didecanoate (4alphaPDD). Although several regulatory sites controlling TRPV4 channel activity have been identified, very little is known about the regulation of TRPV4 expression, a situation common to other TRP channels. Here we show that TRPV4 expression is under the control of progesterone in both human airways and mammary gland epithelial cells, as well as in vascular smooth muscle cells. Exposure of human airways epithelial CFT1-LCFSN and mammary gland epithelial T47D cells to progesterone decreased TRPV4 mRNA and protein expression. Consequently, 4alphaPDD-induced cationic currents and Ca2+ signals were also diminished in progesterone-treated cells. The effect of progesterone was reverted by the progesterone receptor (PR) antagonist RU-486 or following transfection with small interference RNA (siRNA) against both PRA and PRB isoforms. Interestingly, TRPV4 expression and activity were increased in T47D mammary gland epithelial cells when PR was silenced with siRNA. Transcriptional regulation of -1.3 kB TRPV4 promoter-luciferase plasmids was also evaluated in vascular smooth muscle cells. TRPV4 promoter activity was reduced by coexpression with PR and further reduced in the presence of PG. Together, our data report the regulation of TRPV4 expression by progesterone, a process that requires a functional PR.

Regulation of TRP channels by steroids: Implications in physiology and diseases

“…All these effects may be implicated in decidualization, which is an ovarian steroid-induced remodeling/differentiation of the uterus essential for embryo implantation and placentation. In contrast, in human airways, mammary gland epithelial cells and vascular smooth muscle cells TRPV4 is down-regulated by P4 (Jung et al, 2009). Taken together, the results strongly suggest that expression of TRPs in different cells and tissues are tightly regulated by steroids.…”

Sex Hormone–Dependent Regulation of Cilia Beat Frequency in Airway Epithelium

“…Factors that control PR-mediated CBF in oviduct and lung are unknown; however, one potential regulator of CBF is the cilia-based protein known as transient receptor potential cation channel subfamily V member V4, which binds and is regulated by PR (39). Transient receptor potential cation channel subfamily V member V4 is a nonselective calcium channel that increases intracellular calcium and CBF in response to shear stress and increased viscosity (39).…”

“…Transient receptor potential cation channel subfamily V member V4 is a nonselective calcium channel that increases intracellular calcium and CBF in response to shear stress and increased viscosity (39). Several other intracellular signals have been demonstrated to mediate changes of CBF in response to stimuli, including b-adrenergic agonists, nitric oxide, and calcium (40)(41)(42).…”

Effect of osmotic stress on the expression of TRPV4 and BKCa channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes

“…Expression of TRPV4 and BK Ca channels varies be-tween tissues and cell types and was recently demonstrated in equine chondrocytes in vivo and in vitro (16). Expression of these channels at the mRNA and protein levels closely correlates with their activity (20,49). Markedly altered levels of the functional proteins for these channels are associated with disease states (11,32,50).…”