Dataset Information

Canonical Wnt/?-catenin signaling mediates transforming growth factor-?1-driven podocyte injury and proteinuria.

ABSTRACT: Transforming growth factor-?1 (TGF-?1) upregulation occurs in virtually all chronic kidney diseases and is associated with podocyte injury and proteinuria; however, the mechanisms contributing to this in vivo are ambiguous. In vitro, incubation of podocytes with TGF-?1 induced Wnt1 expression, ?-catenin activation, and stimulated the expression of Wnt/?-catenin downstream target genes. Ectopic expression of Wnt1 or ?-catenin mimicked TGF-?1, induced Snail1, and suppressed nephrin expression. The Wnt antagonist, Dickkopf-1, blocked TGF-?1-induced ?-catenin activation, Snail1 induction, and nephrin suppression. In vivo, ectopic expression of TGF-?1 induced Wnt1 expression, activated ?-catenin, and upregulated Wnt target genes such as Snail1, MMP-7, MMP-9, desmin, Fsp1, and PAI-1 in mouse glomeruli, leading to podocyte injury and albuminuria. Consistently, concomitant expression of Dickkopf-1 gene abolished ?-catenin activation, inhibited TGF-?1-triggered Wnt target gene expression, and mitigated albuminuria. Thus, canonical Wnt/?-catenin signaling mediates TGF-?1-driven podocyte injury and proteinuria. These studies suggest that Wnt/?-catenin signaling may be exploited as a therapeutic target for the treatment of proteinuric kidney diseases.

SUBMITTER: Wang D

PROVIDER: S-EPMC4300105 | biostudies-other | 2011 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Canonical Wnt/β-catenin signaling mediates transforming growth factor-β1-driven podocyte injury and proteinuria.

Wang Dan D Dai Chunsun C Li Yingjian Y Liu Youhua Y

Kidney international 20110810 11

Transforming growth factor-β1 (TGF-β1) upregulation occurs in virtually all chronic kidney diseases and is associated with podocyte injury and proteinuria; however, the mechanisms contributing to this in vivo are ambiguous. In vitro, incubation of podocytes with TGF-β1 induced Wnt1 expression, β-catenin activation, and stimulated the expression of Wnt/β-catenin downstream target genes. Ectopic expression of Wnt1 or β-catenin mimicked TGF-β1, induced Snail1, and suppressed nephrin expression. The ...[more]

PMID: 21832980

Similar Datasets

Project description:BackgroundDiabetic nephropathy (DN) is one of the principal complications of diabetes and podocyte injury plays an important role in the DN pathogenesis. Wnt/β-catenin signaling overactivation confers podocyte injury and promotes multiple types of renal disease. However, the underlying mechanism of Wnt/β-catenin signaling activation in DN progression has not been fully elucidated. Long noncoding RNA (lncRNA) is a large class of endogenous RNA molecules lacking functional code capacity and which participates in the pathogenesis of human disease, including DN.MethodA diabetes model was constructed by intraperitoneal injection of Streptozotocin in rats. The MPC5 cells were used to create the in vitro model. Western blot and Quantitative reverse-transcriptase-PCR were used to examine the expression of protein and mRNA. The migrated capacity was analyzed by Transwell migration assay. The cell viability was detected by CCK8.ResultsIn the present study, we revealed the association of lncRNA Maternally Expressed Gene 3 (MEG3) with aberrant activation of Wnt/β-catenin signaling and the role of MEG3/Wnt axis in podocyte injury. We found that high glucose (HG) treatment suppressed MEG3 expression in cultured podocytes, activated Wnt/β-catenin signaling and caused podocyte injury as indicated by the downregulation of podocyte-specific markers (podocin and synaptopodin) and the upregulation of snail1 and α-smooth muscle actin. Overexpression of MEG3 attenuated HG-induced podocyte injury by reducing Wnt/β-catenin activity, repressing cell migration, reactive oxygen species production and increasing the viability of podocytes. Furthermore, we provided evidences that restoration of Wnt/β-catenin signaling by specific agonist impeded the protective effect of MEG3 on podocyte injury. Current results demonstrated that MEG3/Wnt axis plays an important role in fostering podocyte injury and may serve as a potential therapeutic target for the treatment of DN.ConclusionlncRNA MEG3 ameliorates podocyte injury in DN via inactivating Wnt/β-catenin signaling.

Dataset Information

Canonical Wnt/?-catenin signaling mediates transforming growth factor-?1-driven podocyte injury and proteinuria.

Publications

Canonical Wnt/β-catenin signaling mediates transforming growth factor-β1-driven podocyte injury and proteinuria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets