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dc.contributor.author
Numaga-Tomita, Takuro
dc.contributor.author
Shimauchi, Tsukasa
dc.contributor.author
Oda, Sayaka
dc.contributor.author
Tanaka, Tomohiro
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Nishiyama, Kazuhiro
dc.contributor.author
Nishimura, Akiyuki
dc.contributor.author
Birnbaumer, Lutz
dc.contributor.author
Mori, Yasuo
dc.contributor.author
Nishida, Motohiro
dc.date.available
2020-12-16T15:10:52Z
dc.date.issued
2019-09
dc.identifier.citation
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
dc.identifier.issn
0892-6638
dc.identifier.uri
http://hdl.handle.net/11336/120569
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Federation of American Societies for Experimental Biology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CA2+ CHANNEL
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MEMBRANE POTENTIAL
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PHENOTYPE SWITCHING
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TRANSIENT RECEPTOR POTENTIAL
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VSMCS
dc.subject.classification
Biología Celular, Microbiología
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-25T16:38:11Z
dc.journal.volume
33
dc.journal.number
9
dc.journal.pagination
9785-9796
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Numaga-Tomita, Takuro. No especifíca;
dc.description.fil
Fil: Shimauchi, Tsukasa. Kyushu University; Japón
dc.description.fil
Fil: Oda, Sayaka. No especifíca;
dc.description.fil
Fil: Tanaka, Tomohiro. No especifíca;
dc.description.fil
Fil: Nishiyama, Kazuhiro. Kyushu University; Japón
dc.description.fil
Fil: Nishimura, Akiyuki. Kyushu University; Japón
dc.description.fil
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
dc.description.fil
Fil: Mori, Yasuo. No especifíca;
dc.description.fil
Fil: Nishida, Motohiro. Kyushu University; Japón
dc.journal.title
FASEB Journal
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1096/fj.201802811R
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