The farnesoid x receptor agonist edp-305 reduces interstitial renal fibrosis in a mouse model of unilateral ureteral obstruction.

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dc.creatorShen li
dc.creatorPeter Caravan
dc.creatorKenneth K. Tanabe
dc.creatorBryan C. Fuchs
dc.creatorSarani Ghoshal
dc.creatorMozhdeh Soojodi
dc.creatorGunisha Arora
dc.creatorDiêgo dos Santos Ferreira
dc.creatorDerek J. Erstad
dc.creatorLi-Juan Jiang
dc.creatorRicard Masia
dc.creatorMichael Lanuti
dc.creatorYang Li
dc.creatorGuogiang Wang
dc.creatorYat Sun Or
dc.date.accessioned2024-07-09T16:07:45Z
dc.date.accessioned2025-09-09T01:21:59Z
dc.date.available2024-07-09T16:07:45Z
dc.date.issued2019-06
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1096/fj.201801699R
dc.identifier.issn1530-6860
dc.identifier.urihttps://hdl.handle.net/1843/69880
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.rightsAcesso Restrito
dc.subjectRim
dc.subjectInsuficiência renal crônica
dc.subjectFibrose renal
dc.subject.otherFXR
dc.subject.otherKidney
dc.subject.otherInjury
dc.subject.otherUUO
dc.subject.otherYAP1
dc.titleThe farnesoid x receptor agonist edp-305 reduces interstitial renal fibrosis in a mouse model of unilateral ureteral obstruction.
dc.typeArtigo de periódico
local.citation.epage7112
local.citation.spage7103
local.citation.volume33
local.description.resumoFarnesoid X receptor (FXR) is a nuclear receptor that has emerged as a key regulator in the maintenance ofhepatic steatosis, inflammation, and fibrosis. However, the role of FXR in renal fibrosis remains to be established.Here, we investigate the effects of the FXR agonist EDP-305 in a mouse model of tubulointerstitial fibrosis viaunilateral ureteral obstruction (UUO). Male C57Bl/6 mice received a UUO on their left kidney. On postoperative d 4,mice received daily treatment by oral gavage with either vehicle control (0.5% methylcellulose) or 10 or 30 mg/kgEDP-305. All animals were euthanized on postoperative d 12. EDP-305 dose-dependently decreased macrophageinfiltration as measured by the F4/80 staining area and proinflammatory cytokine gene expression. EDP-305 alsodose-dependently reduced interstitial fibrosis as assessed by morphometric quantification of the collagen pro-portional area and kidney hydroxyproline levels. Finally, yes-associated protein (YAP) activation, a major driver offibrosis, increased after UUO injury and was diminished by EDP-305 treatment. Consistently, EDP-305 decreasedTGF-b1–induced YAP nuclear localization in human kidney 2 cells by increasing inhibitory YAP phosphorylation.YAP inhibition may be a novel antifibrotic mechanism of FXR agonism, and EDP-305 could be used to treat renalfibrosis.—Li, S., Ghoshal, S., Sojoodi, M., Arora, G., Masia, R., Erstad, D. J., Ferriera, D. S., Li, Y., Wang, G., Lanuti,M., Caravan, P., Or, Y. S., Jiang, L.-J., Tanabe, K. K., Fuchs, B. C. The farnesoid X receptor agonist EDP-305 reducesinterstitial renal fibrosis in a mouse model of unilateral ureteral obstruction.
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
local.publisher.initialsUFMG
local.url.externahttps://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201801699R

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