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dc.contributor.author
Numaga Tomita, Takuro
dc.contributor.author
Kitajima, Naoyuki
dc.contributor.author
Kuroda, Takuya
dc.contributor.author
Nishimura, Akiyuki
dc.contributor.author
Miyano, Kei
dc.contributor.author
Yasuda, Satoshi
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Kuwahara, Koichiro
dc.contributor.author
Sato, Yoji
dc.contributor.author
Ide, Tomomi
dc.contributor.author
Birnbaumer, Lutz
dc.contributor.author
Sumimoto, Hideki
dc.contributor.author
Mori, Yasuo
dc.contributor.author
Nishida, Motohiro
dc.date.available
2018-07-10T19:01:38Z
dc.date.issued
2016-12
dc.identifier.citation
Numaga Tomita, Takuro; Kitajima, Naoyuki; Kuroda, Takuya; Nishimura, Akiyuki; Miyano, Kei; et al.; TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis; Nature Publishing Group; Scientific Reports; 6; 12-2016; 1-15; 39383
dc.identifier.uri
http://hdl.handle.net/11336/51651
dc.description.abstract
Structural cardiac remodeling, accompanying cytoskeletal reorganization of cardiac cells, is a major clinical outcome of diastolic heart failure. A highly local Ca2+ influx across the plasma membrane has been suggested to code signals to induce Rho GTPase-mediated fibrosis, but it is obscure how the heart specifically decodes the local Ca2+ influx as a cytoskeletal reorganizing signal under the conditions of the rhythmic Ca2+ handling required for pump function. We found that an inhibition of transient receptor potential canonical 3 (TRPC3) channel activity exhibited resistance to Rho-mediated maladaptive fibrosis in pressure-overloaded mouse hearts. Proteomic analysis revealed that microtubule-associated Rho guanine nucleotide exchange factor, GEF-H1, participates in TRPC3-mediated RhoA activation induced by mechanical stress in cardiomyocytes and transforming growth factor (TGF) β stimulation in cardiac fibroblasts. We previously revealed that TRPC3 functionally interacts with microtubule-associated NADPH oxidase (Nox) 2, and inhibition of Nox2 attenuated mechanical stretch-induced GEF-H1 activation in cardiomyocytes. Finally, pharmacological TRPC3 inhibition significantly suppressed fibrotic responses in human cardiomyocytes and cardiac fibroblasts. These results strongly suggest that microtubule-localized TRPC3-GEF-H1 axis mediates fibrotic responses commonly in cardiac myocytes and fibroblasts induced by physico-chemical stimulation.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Trpc3
dc.subject
Gef-H1
dc.subject
Rho
dc.subject
Heart Failure
dc.subject.classification
Inmunología
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-06T19:40:53Z
dc.identifier.eissn
2045-2322
dc.journal.volume
6
dc.journal.pagination
1-15; 39383
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Numaga Tomita, Takuro. Graduate University for Advanced Studies; Japón. National Institutes of Natural Sciences; Japón
dc.description.fil
Fil: Kitajima, Naoyuki. Graduate University for Advanced Studies; Japón. Kyushu University; Japón
dc.description.fil
Fil: Kuroda, Takuya. National Institute of Health Sciences; Japón
dc.description.fil
Fil: Nishimura, Akiyuki. National Institutes of Natural Sciences; Japón. Graduate University for Advanced Studies; Japón
dc.description.fil
Fil: Miyano, Kei. Kyushu University; Japón
dc.description.fil
Fil: Yasuda, Satoshi. National Institute of Health Sciences; Japón
dc.description.fil
Fil: Kuwahara, Koichiro. Shinshu University; Japón
dc.description.fil
Fil: Sato, Yoji. Kyushu University; Japón. National Institute of Health Sciences; Japón
dc.description.fil
Fil: Ide, Tomomi. Kyushu University; Japón
dc.description.fil
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina ; Argentina. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Sumimoto, Hideki. Kyushu University; Japón
dc.description.fil
Fil: Mori, Yasuo. Kyoto University; Japón
dc.description.fil
Fil: Nishida, Motohiro. Kyushu University; Japón. National Institutes of Natural Sciences; Japón. Graduate University for Advanced Studies; Japón
dc.journal.title
Scientific Reports
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/srep39383
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1038/srep39383
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