TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN

Autores
Numaga-Tomita, Takuro; Shimauchi, Tsukasa; Oda, Sayaka; Tanaka, Tomohiro; Nishiyama, Kazuhiro; Nishimura, Akiyuki; Birnbaumer, Lutz; Mori, Yasuo; Nishida, Motohiro
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Vascular smooth muscle cells (VSMCs) play critical roles in the stability and tonic regulation of vascular homeostasis. VSMCs can switch back and forth between highly proliferative synthetic and fully differentiated contractile phenotypes in response to changes in the vessel environment. Although abnormal phenotypic switching of VSMCs is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty, how control of VSMC phenotypic switching is dysregulated in pathologic conditions remains obscure. We found that inhibition of canonical transient receptor potential 6 (TRPC6) channels facilitated contractile differentiation of VSMCs through plasma membrane hyperpolarization. TRPC6-deficient VSMCs exhibited more polarized resting membrane potentials and higher protein kinase B (Akt) activity than wild-type VSMCs in response to TGF-β1 stimulation. Ischemic stress elicited by oxygen-glucose deprivation suppressed TGF-β1-induced hyperpolarization and VSMC differentiation, but this effect was abolished by TRPC6 deletion. TRPC6-mediated Ca2+ influx and depolarization coordinately promoted the interaction of TRPC6 with lipid phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of Akt activation. Given the marked up-regulation of TRPC6 observed in vascular disorders, our findings suggest that attenuation of TRPC6 channel activity in pathologic VSMCs could be a rational strategy to maintain vascular quality control by fine-tuning of VSMC phenotypic switching.
Fil: Numaga-Tomita, Takuro. No especifíca;
Fil: Shimauchi, Tsukasa. Kyushu University; Japón
Fil: Oda, Sayaka. No especifíca;
Fil: Tanaka, Tomohiro. No especifíca;
Fil: Nishiyama, Kazuhiro. Kyushu University; Japón
Fil: Nishimura, Akiyuki. Kyushu University; Japón
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Mori, Yasuo. No especifíca;
Fil: Nishida, Motohiro. Kyushu University; Japón
Materia
CA2+ CHANNEL
MEMBRANE POTENTIAL
PHENOTYPE SWITCHING
TRANSIENT RECEPTOR POTENTIAL
VSMCS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/120569
Acceder
id CONICETDig_fa8649da54bc6c73d67562236267ff0e
oai_identifier_str oai:ri.conicet.gov.ar:11336/120569
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTENNumaga-Tomita, TakuroShimauchi, TsukasaOda, SayakaTanaka, TomohiroNishiyama, KazuhiroNishimura, AkiyukiBirnbaumer, LutzMori, YasuoNishida, MotohiroCA2+ CHANNELMEMBRANE POTENTIALPHENOTYPE SWITCHINGTRANSIENT RECEPTOR POTENTIALVSMCShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Vascular smooth muscle cells (VSMCs) play critical roles in the stability and tonic regulation of vascular homeostasis. VSMCs can switch back and forth between highly proliferative synthetic and fully differentiated contractile phenotypes in response to changes in the vessel environment. Although abnormal phenotypic switching of VSMCs is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty, how control of VSMC phenotypic switching is dysregulated in pathologic conditions remains obscure. We found that inhibition of canonical transient receptor potential 6 (TRPC6) channels facilitated contractile differentiation of VSMCs through plasma membrane hyperpolarization. TRPC6-deficient VSMCs exhibited more polarized resting membrane potentials and higher protein kinase B (Akt) activity than wild-type VSMCs in response to TGF-β1 stimulation. Ischemic stress elicited by oxygen-glucose deprivation suppressed TGF-β1-induced hyperpolarization and VSMC differentiation, but this effect was abolished by TRPC6 deletion. TRPC6-mediated Ca2+ influx and depolarization coordinately promoted the interaction of TRPC6 with lipid phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of Akt activation. Given the marked up-regulation of TRPC6 observed in vascular disorders, our findings suggest that attenuation of TRPC6 channel activity in pathologic VSMCs could be a rational strategy to maintain vascular quality control by fine-tuning of VSMC phenotypic switching.Fil: Numaga-Tomita, Takuro. No especifíca;Fil: Shimauchi, Tsukasa. Kyushu University; JapónFil: Oda, Sayaka. No especifíca;Fil: Tanaka, Tomohiro. No especifíca;Fil: Nishiyama, Kazuhiro. Kyushu University; JapónFil: Nishimura, Akiyuki. Kyushu University; JapónFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Mori, Yasuo. No especifíca;Fil: Nishida, Motohiro. Kyushu University; JapónFederation of American Societies for Experimental Biology2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/120569Numaga-Tomita, Takuro; Shimauchi, Tsukasa; Oda, Sayaka; Tanaka, Tomohiro; Nishiyama, Kazuhiro; et al.; TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN; Federation of American Societies for Experimental Biology; FASEB Journal; 33; 9; 9-2019; 9785-97960892-6638CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1096/fj.201802811Rinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:49Zoai:ri.conicet.gov.ar:11336/120569instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:49.941CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
title TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
spellingShingle TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
Numaga-Tomita, Takuro
CA2+ CHANNEL
MEMBRANE POTENTIAL
PHENOTYPE SWITCHING
TRANSIENT RECEPTOR POTENTIAL
VSMCS
title_short TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
title_full TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
title_fullStr TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
title_full_unstemmed TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
title_sort TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
dc.creator.none.fl_str_mv Numaga-Tomita, Takuro
Shimauchi, Tsukasa
Oda, Sayaka
Tanaka, Tomohiro
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
author Numaga-Tomita, Takuro
author_facet Numaga-Tomita, Takuro
Shimauchi, Tsukasa
Oda, Sayaka
Tanaka, Tomohiro
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
author_role author
author2 Shimauchi, Tsukasa
Oda, Sayaka
Tanaka, Tomohiro
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CA2+ CHANNEL
MEMBRANE POTENTIAL
PHENOTYPE SWITCHING
TRANSIENT RECEPTOR POTENTIAL
VSMCS
topic CA2+ CHANNEL
MEMBRANE POTENTIAL
PHENOTYPE SWITCHING
TRANSIENT RECEPTOR POTENTIAL
VSMCS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Vascular smooth muscle cells (VSMCs) play critical roles in the stability and tonic regulation of vascular homeostasis. VSMCs can switch back and forth between highly proliferative synthetic and fully differentiated contractile phenotypes in response to changes in the vessel environment. Although abnormal phenotypic switching of VSMCs is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty, how control of VSMC phenotypic switching is dysregulated in pathologic conditions remains obscure. We found that inhibition of canonical transient receptor potential 6 (TRPC6) channels facilitated contractile differentiation of VSMCs through plasma membrane hyperpolarization. TRPC6-deficient VSMCs exhibited more polarized resting membrane potentials and higher protein kinase B (Akt) activity than wild-type VSMCs in response to TGF-β1 stimulation. Ischemic stress elicited by oxygen-glucose deprivation suppressed TGF-β1-induced hyperpolarization and VSMC differentiation, but this effect was abolished by TRPC6 deletion. TRPC6-mediated Ca2+ influx and depolarization coordinately promoted the interaction of TRPC6 with lipid phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of Akt activation. Given the marked up-regulation of TRPC6 observed in vascular disorders, our findings suggest that attenuation of TRPC6 channel activity in pathologic VSMCs could be a rational strategy to maintain vascular quality control by fine-tuning of VSMC phenotypic switching.
Fil: Numaga-Tomita, Takuro. No especifíca;
Fil: Shimauchi, Tsukasa. Kyushu University; Japón
Fil: Oda, Sayaka. No especifíca;
Fil: Tanaka, Tomohiro. No especifíca;
Fil: Nishiyama, Kazuhiro. Kyushu University; Japón
Fil: Nishimura, Akiyuki. Kyushu University; Japón
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Mori, Yasuo. No especifíca;
Fil: Nishida, Motohiro. Kyushu University; Japón
description Vascular smooth muscle cells (VSMCs) play critical roles in the stability and tonic regulation of vascular homeostasis. VSMCs can switch back and forth between highly proliferative synthetic and fully differentiated contractile phenotypes in response to changes in the vessel environment. Although abnormal phenotypic switching of VSMCs is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty, how control of VSMC phenotypic switching is dysregulated in pathologic conditions remains obscure. We found that inhibition of canonical transient receptor potential 6 (TRPC6) channels facilitated contractile differentiation of VSMCs through plasma membrane hyperpolarization. TRPC6-deficient VSMCs exhibited more polarized resting membrane potentials and higher protein kinase B (Akt) activity than wild-type VSMCs in response to TGF-β1 stimulation. Ischemic stress elicited by oxygen-glucose deprivation suppressed TGF-β1-induced hyperpolarization and VSMC differentiation, but this effect was abolished by TRPC6 deletion. TRPC6-mediated Ca2+ influx and depolarization coordinately promoted the interaction of TRPC6 with lipid phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of Akt activation. Given the marked up-regulation of TRPC6 observed in vascular disorders, our findings suggest that attenuation of TRPC6 channel activity in pathologic VSMCs could be a rational strategy to maintain vascular quality control by fine-tuning of VSMC phenotypic switching.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/120569
Numaga-Tomita, Takuro; Shimauchi, Tsukasa; Oda, Sayaka; Tanaka, Tomohiro; Nishiyama, Kazuhiro; et al.; TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN; Federation of American Societies for Experimental Biology; FASEB Journal; 33; 9; 9-2019; 9785-9796
0892-6638
CONICET Digital
CONICET
url http://hdl.handle.net/11336/120569
identifier_str_mv Numaga-Tomita, Takuro; Shimauchi, Tsukasa; Oda, Sayaka; Tanaka, Tomohiro; Nishiyama, Kazuhiro; et al.; TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN; Federation of American Societies for Experimental Biology; FASEB Journal; 33; 9; 9-2019; 9785-9796
0892-6638
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.201802811R
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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