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dc.contributor.author
Wu, Yueh-Lin
dc.contributor.author
Xie, Jian
dc.contributor.author
An, Sung-Wan
dc.contributor.author
Oliver, Noelynn
dc.contributor.author
Barrezueta, Nestor X.
dc.contributor.author
Lin, Mei-Hsiang
dc.contributor.author
Birnbaumer, Lutz
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dc.contributor.author
Huang, Chou-Long
dc.date.available
2018-06-08T15:06:03Z
dc.date.issued
2017-04
dc.identifier.citation
Wu, Yueh-Lin; Xie, Jian; An, Sung-Wan; Oliver, Noelynn; Barrezueta, Nestor X.; et al.; Inhibition of TRPC6 channels ameliorates renal fibrosis and contributes to renal protection by soluble klotho; Nature Publishing Group; Kidney International; 91; 4; 4-2017; 830-841
dc.identifier.issn
0085-2538
dc.identifier.uri
http://hdl.handle.net/11336/47862
dc.description.abstract
Fibrosis is an exaggerated form of tissue repair that occurs with serious damage or repetitive injury and ultimately leads to organ failure due to the excessive scarring. Increased calcium ion entry through the TRPC6 channel has been associated with the pathogenesis of heart and glomerular diseases, but its role in renal interstitial fibrosis is unknown. We studied this by deletion of Trpc6 in mice and found it decreased unilateral ureteral obstruction-induced interstitial fibrosis and blunted increased mRNA expression of fibrosis-related genes in the ureteral obstructed kidney relative to that in the kidney of wild-type mice. Administration of BTP2, a pyrazol derivative known to inhibit function of several TRPC channels, also ameliorated obstruction-induced renal fibrosis and gene expression in wild-type mice. BTP2 inhibited carbachol-activated TRPC3 and TRPC6 channel activities in HEK293 cells. Ureteral obstruction caused over a 10-fold increase in mRNA expression for TRPC3 as well as TRPC6 in the kidneys of obstructed relative to the sham-operated mice. The magnitude of protection against obstruction-induced fibrosis in Trpc3 and Trpc6 double knockout mice was not different from that in Trpc6 knockout mice. Klotho, a membrane and soluble protein predominantly produced in the kidney, is known to confer protection against renal fibrosis. Administration of soluble klotho significantly reduced obstruction-induced renal fibrosis in wild-type mice, but not in Trpc6 knockout mice, indicating that klotho and TRPC6 inhibition act in the same pathway to protect against obstruction-induced renal fibrosis. Thus klotho and TRPC6 may be pharmacologic targets for treating renal fibrosis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Btp2
dc.subject
Fibrosis
dc.subject
Klotho
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Trpc3
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Trpc6
dc.subject
Uuo
dc.subject.classification
Inmunología
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Inhibition of TRPC6 channels ameliorates renal fibrosis and contributes to renal protection by soluble klotho
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-07T14:08:58Z
dc.journal.volume
91
dc.journal.number
4
dc.journal.pagination
830-841
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Wu, Yueh-Lin. University of Texas Southwestern Medical Center; Estados Unidos. Taipei Medical University Hospital; China. Taipei Medical University; China
dc.description.fil
Fil: Xie, Jian. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: An, Sung-Wan. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: Oliver, Noelynn. Boehringer Ingelheim Pharmaceuticals Inc.; Estados Unidos
dc.description.fil
Fil: Barrezueta, Nestor X.. Boehringer Ingelheim Pharmaceuticals Inc.; Estados Unidos
dc.description.fil
Fil: Lin, Mei-Hsiang. Taipei Medical University; China
dc.description.fil
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina ; Argentina. Research Triangle Park; Estados Unidos
dc.description.fil
Fil: Huang, Chou-Long. University of Texas Southwestern Medical Center; Estados Unidos
dc.journal.title
Kidney International
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.kint.2016.09.039
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0085253816305919
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