Epithelial-Mesenchymal Transition gene database (dbEMT) Home
Pediatric cancer database
General information | Literature | Expression | Regulation | Mutation | Interaction

Basic Information

Gene ID





AWT1|EWS-WT1|GUD|NPHS4|WAGR|WIT-2|WT33;Wilms tumor 1;WT1;Wilms tumor 1


Wilms tumor protein|amino-terminal domain of EWS|last three zinc fingers of the DNA-binding domain of WT1



Gene type




WT1 and Pax2 re-expression is required for epithelial-mesenchymal transition in 5/6 nephrectomized rats and cultured kidney tubular epithelial cells.

Mature tubular epithelial cells in the adult kidney can undergo epithelial-mesenchymal transition (EMT), a phenotypic change that is linked to the pathogenesis of renal interstitial fibrosis. EMT may be considered the reverse of mesenchymal-epithelial transition, which occurs during normal kidney development. The Wilms' tumor suppressor gene WT1 and the paired box 2 gene Pax2 are needed to induce mesenchymal-epithelial transition and play key roles in the progression of nephrogenesis. However, until now, WT1 and Pax2 have not been tested for their direct involvement in the process of renal tubular EMT. In this study, we explored the potential roles of WT1 and Pax2 in EMT that is induced in the remnant kidney of rats following 5/6 nephrectomy. We also examined WT1 and Pax2 in cultured renal tubular epithelial (NRK52E) cells treated with interleukin-1alpha and investigated the effects of blocking EMT using RNA interference. We showed that WT1 and Pax2 were re-expressed in the EMT models, and these were accompanied by decreased expression of E-cadherin and increased expression of vimentin, Snail and alpha-smooth muscle actin. Silencing WT1 and Pax2 by RNA interference blocked the interleukin-1alpha-induced EMT in the NRK52E cells, as reflected in the suppression of alpha-SMA and Snail expression, the restoration of E-cadherin expression and normal cell morphology. Our experiments suggested that the re-expression of WT1 and Pax2 in the tubular epithelial cells plays important roles in the promotion of EMT, and there may be therapeutic value in silencing Pax2 and WT1 to prevent or reverse renal fibrosis.CI - Copyright (c) 2011 S. Karger AG, Basel.

WT1 regulates epicardial epithelial to mesenchymal transition through beta-catenin and retinoic acid signaling pathways.

An epithelial sheet, the epicardium, lines the surface of the heart. In the developing embryo, the epicardium expresses the transcriptional regulator Wilm's tumor Gene 1 (Wt1). Through incompletely understood mechanisms, Wt1 inactivation derails normal heart development. We investigated mechanisms by which Wt1 regulates heart development and epicardial epithelial to mesenchymal transition (EMT). We used genetic lineage tracing approaches to track and isolate epicardium and epicardium derivatives in hearts lacking Wt1 (Wt1(KO)). Wt1(KO) hearts had diminished proliferation of compact myocardium and impaired coronary plexus formation. Wt1(KO) epicardium failed to undergo EMT. Wt1(KO) epicardium expressed reduced Lef1 and Ctnnb1 (beta-catenin), key components of the canonical Wnt/beta-catenin signaling pathway. Wt1(KO) epicardium expressed decreased levels of canonical Wnt downstream targets Axin2, Cyclin D1, and Cyclin D2 and exhibited decreased activity of the Batgal Wnt/beta-catenin reporter transgene, suggestive of diminished canonical Wnt signaling. Hearts with epicardium-restricted Ctnnb1 loss of function resembled Wt1(KO) hearts and also failed to undergo epicardial EMT. However, Ctnnb1 inactivation did not alter WT1 expression, positioning Wt1 upstream of canonical Wnt/beta-catenin signaling. Wnt5a, a prototypic non-canonical Wnt with enriched epicardial expression, and Raldh2, a key regulator of retinoic acid signaling confined to the epicardium, were also markedly downregulated in Wt1(KO) epicardium. Hearts lacking Wnt5a or Raldh2 shared phenotypic features with Wt1(KO). Although Wt1 has been proposed to regulate EMT by repressing E-cadherin, we detected no change in E-cadherin in Wt1(KO) epicardium. Collectively, our study shows that Wt1 regulates epicardial EMT and heart development through canonical Wnt, non-canonical Wnt, and retinoic acid signaling pathways.CI - Copyright (c) 2011 Elsevier Inc. All rights reserved.