The progesterone receptor regulates the expression of TRPV4 channel

Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Edifici PRBB, Parc de Recerca Biomèdica de Barcelona, Room 343, C/Dr. Aiguader 88, Barcelona, 08003, Spain.
Pflügers Archiv - European Journal of Physiology (Impact Factor: 4.1). 09/2009; 459(1):105-13. DOI: 10.1007/s00424-009-0706-7
Source: PubMed


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.

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Available from: Carole Jung
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    • "A similar current-voltage relationship was demonstrated in mutated TRPV4 channels [69], in which both aspartates in the TRPV4 pore region were neutralized, causing a marked reduction in outward rectification. Moreover, a modest outward/inward rectification was also shown in HEK293 cells expressing human TRPV4 [70] and in human airway epithelial CFT1-LCFSN cells [71]. Since it is not obvious what underlies the linear TRPV4 current-voltage relationship in adult astrocytes, we hypothesize that post-translational modifications, conformational changes of the TRPV4 protein or protein-protein interactions might contribute to such current behavior. "
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