Glycogen synthase kinase-3 inactivation and stabilization of β-catenin induce nephron differentiation in isolated mouse and rat kidney mesenchymes

被引:106
|
作者
Kuure, Satu
Popsueva, Anna
Jakobson, Madis
Sainio, Kirsi
Sariola, Hannu
机构
[1] Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland
[2] Univ Helsinki, Cent Hosp, HusLab, FIN-00014 Helsinki, Finland
[3] Univ Tartu, Inst Zool & Hydrobiol, Dept Dev Biol, EE-50090 Tartu, Estonia
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2007年 / 18卷 / 04期
关键词
D O I
10.1681/ASN.2006111206
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Wnt proteins are required for induction of nephrons in mouse metanephric kidneys, but the downstream pathways that mediate tubule induction and epithelial differentiation have remained obscure. The intracellular mechanisms by which Wnt signaling mediates nephron induction in embryonic kidney mesenchymes were studied. First is shown that transient exposure of isolated kidney mesenchymes to structurally different glycogen synthase kinase-3 (GSK3) inhibitors lithium or 6-bromoindirubin-3'-oxime results in abundant epithelial differentiation and full segregation of nephrons. Shown further by mice with genetically disrupted ureteric bud or Wolffian duct development is that this nephrogenic competence arises independent of the influence of Wolffian duct-derived epithelia. Analysis of the intracellular signaling cascades downstream of GSK3 inhibition revealed stabilization of beta-catenin and upregulation of Lef1 and Tcf1, both events that are associated with the active canonical Wnt signaling. Last, genetic evidence that metanephric mesenchyme-specific stabilization of beta-catenin is sufficient to induce nephron differentiation in isolated kidney mesenchymes, similar to that induced by GSK3 inhibitors, is provided. These data show that activation of canonical Wnt pathway is sufficient to induce nephrogenesis and suggest that this pathway mediates the nephron induction in murine kidney mesenchymes.
引用
收藏
页码:1130 / 1139
页数:10
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