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

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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. A...

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Autores principales: Numaga-Tomita, Takuro, Tsukasa, Shimauchi, Oda, Sayaka, Tanaka, Tomohiro, Nishiyama, Kazuhiro, Nishimura, Akiyuki, Birnbaumer, Lutz, Mori, Yasuo, Nishida, Motohiro
Formato: Artículo
Lenguaje:Inglés
Publicado: Federation of American Societies for Experimental Biology 2020
Materias:
VASOS SANGUINEOS
TONO VASCULAR
ENFERMEDADES CARDIOVASCULARES
HOMEOSTASIS
ENDOTELIO
CANALES IONICOS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/9531
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-9531
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic VASOS SANGUINEOS
TONO VASCULAR
ENFERMEDADES CARDIOVASCULARES
HOMEOSTASIS
ENDOTELIO
CANALES IONICOS
spellingShingle VASOS SANGUINEOS
TONO VASCULAR
ENFERMEDADES CARDIOVASCULARES
HOMEOSTASIS
ENDOTELIO
CANALES IONICOS
Numaga-Tomita, Takuro
Tsukasa, Shimauchi
Oda, Sayaka
Tanaka, Tomohiro
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
topic_facet VASOS SANGUINEOS
TONO VASCULAR
ENFERMEDADES CARDIOVASCULARES
HOMEOSTASIS
ENDOTELIO
CANALES IONICOS
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.-Numaga-Tomita, T., Shimauchi, T., Oda, S., Tanaka, T., Nishiyama, K., Nishimura, A., Birnbaumer, L., Mori, Y., Nishida, M. TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN.
format Artículo
author Numaga-Tomita, Takuro
Tsukasa, Shimauchi
Oda, Sayaka
Tanaka, Tomohiro
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
author_facet Numaga-Tomita, Takuro
Tsukasa, Shimauchi
Oda, Sayaka
Tanaka, Tomohiro
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
author_sort Numaga-Tomita, Takuro
title TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN
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
publisher Federation of American Societies for Experimental Biology
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/9531
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