title: 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.
authors.affiliation: 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.
authors.forename: Carole
authors.initials: C
authors.lastname: Jung
authors.forename: César
authors.initials: C
authors.lastname: Fandos
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Lorenzo
authors.forename: Cristina
authors.initials: C
authors.lastname: Plata
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fernandes
authors.forename: Gemma G
authors.initials: GG
authors.lastname: Gené
authors.forename: Esther
authors.initials: E
authors.lastname: Vázquez
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valverde
mesh_terms: D015153:Blotting, Western; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018408:Patch-Clamp Techniques; D011374:Progesterone / Q000378:metabolism; D011372:Progestins / Q000378:metabolism; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000096:biosynthesis*
chemical_list: D011372:Progestins; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D011374:Progesterone
references.citation: Pharmacol Rev. 2000 Dec;52(4):513-56
references.pmid: 11121509
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5329-34
references.pmid: 11309505
references.citation: J Biol Chem. 2008 Jan 4;283(1):416-426
references.pmid: 17928298
references.citation: Gen Comp Endocrinol. 1999 Sep;115(3):429-41
references.pmid: 10480995
references.citation: J Biol Chem. 2003 Jun 20;278(25):22664-8
references.pmid: 12692122
references.citation: Am J Physiol. 1993 May;264(5 Pt 1):C1219-30
references.pmid: 7684560
references.citation: Mol Reprod Dev. 2005 Aug;71(4):444-52
references.pmid: 15858826
references.citation: Mol Reprod Dev. 2007 Jul;74(7):843-50
references.pmid: 17154304
references.citation: Circ Res. 2005 Dec 9;97(12):1270-9
references.pmid: 16269659
references.citation: J Biol Chem. 2007 Apr 27;282(17):12796-803
references.pmid: 17341586
references.citation: Mol Endocrinol. 2005 Dec;19(12):3023-37
references.pmid: 16020483
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12611-6
references.pmid: 18719094
references.citation: Acta Otolaryngol. 2004 Oct;124(8):958-963
references.pmid: 15536653
references.citation: J Biol Chem. 2006 Jan 20;281(3):1580-6
references.pmid: 16293632
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Feb;286(2):R233-49
references.pmid: 14707008
references.citation: J Biol Chem. 2006 Jul 28;281(30):20715-20727
references.pmid: 16709572
references.citation: Pflugers Arch. 2003 Jun;446(3):304-8
references.pmid: 12684797
references.citation: Hear Res. 2005 Mar;201(1-2):132-44
references.pmid: 15721568
references.citation: Nat Cell Biol. 2000 Oct;2(10):695-702
references.pmid: 11025659
references.citation: Breast Cancer Res. 2002;4(5):187-90
references.pmid: 12223122
references.citation: Mol Endocrinol. 2001 Dec;15(12):2078-92
references.pmid: 11731610
references.citation: News Physiol Sci. 2001 Dec;16:251-5
references.pmid: 11719599
references.citation: J Endocrinol. 2006 Dec;191(3):525-35
references.pmid: 17170211
references.citation: J Leukoc Biol. 2008 Oct;84(4):924-31
references.pmid: 18664528
references.citation: Nature. 1990 Jun 7;345(6275):547-50
references.pmid: 2348863
references.citation: Am J Physiol Cell Physiol. 2004 Feb;286(2):C195-205
references.pmid: 14707014
references.citation: Circ Res. 2005 Dec 9;97(12):1360-5
references.pmid: 16293791
references.citation: J Biol Chem. 2008 Mar 7;283(10):6272-80
references.pmid: 18174177
references.citation: Hum Reprod. 1998 Nov;13(11):2991-4
references.pmid: 9853843
references.citation: J Biol Chem. 2004 Dec 24;279(52):54062-8
references.pmid: 15489228
references.citation: J Endocrinol. 1994 Aug;142(2):311-6
references.pmid: 7931003
references.citation: J Cell Biol. 2005 Mar 14;168(6):869-74
references.pmid: 15753126
references.citation: Mol Cell Endocrinol. 1997 Nov 30;135(1):79-91
references.pmid: 9453243
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13698-703
references.pmid: 14581612
references.citation: Mol Cancer Ther. 2008 Feb;7(2):271-9
references.pmid: 18245667
references.citation: J Biol Chem. 2008 Nov 14;283(46):31284-8
references.pmid: 18826956
references.citation: Pflugers Arch. 2008 Oct;457(1):149-59
references.pmid: 18458941
references.citation: J Cell Biol. 2008 Apr 7;181(1):143-55
references.pmid: 18378772
references.citation: J Cell Biochem. 1993 Feb;51(2):130-4
references.pmid: 8440746
references.citation: J Biol Chem. 2002 Apr 19;277(16):13569-77
references.pmid: 11827975
references.citation: Neurobiol Aging. 2008 Jul;29(7):969-80
references.pmid: 17306421
references.citation: J Steroid Biochem Mol Biol. 1998 Feb;64(3-4):147-56
references.pmid: 9605409
references.citation: J Biol Chem. 2003 Jul 18;278(29):26541-9
references.pmid: 12724311
references.citation: Science. 1999 Sep 17;285(5435):1929-31
references.pmid: 10489376
references.citation: Toxicol Lett. 2009 Apr 25;186(2):123-9
references.pmid: 19429233
references.citation: J Exp Med. 1998 Nov 2;188(9):1593-602
references.pmid: 9802971
references.citation: J Assist Reprod Genet. 2000 Feb;17(2):103-6
references.pmid: 10806589
references.citation: FEBS Lett. 1997 Oct 6;415(3):335-40
references.pmid: 9357995
references.citation: Steroids. 2009 Aug;74(8):642-9
references.pmid: 19463684
references.citation: Endocr Relat Cancer. 2005 Jun;12(2):367-82
references.pmid: 15947109
references.citation: J Biol Chem. 2003 Aug 29;278(35):33284-9
references.pmid: 12794078
references.citation: J Biol Chem. 2003 Jul 18;278(29):27129-37
references.pmid: 12738791
references.citation: Horm Metab Res. 2004 Mar;36(3):136-41
references.pmid: 15057665
references.citation: Semin Cell Dev Biol. 2006 Dec;17(6):607-17
references.pmid: 17174125
references.citation: Am J Physiol Cell Physiol. 2002 Dec;283(6):C1705-14
references.pmid: 12388065