| Autor: |
Rasouly, Hila Milo, Kumar, Sudhir, Chan, Stefanie, Pisarek-Horowitz, Anna, Sharma, Richa, Xi, Qiongchao J., Nishizaki, Yuriko, Higashi, Yujiro, Salant, David J., Maas, Richard L., Lu, Weining |
| Zdroj: |
Kidney International; December 2016, Vol. 90 Issue: 6 p1262-1273, 12p |
| Abstrakt: |
Primary glomerulocystic kidney disease is a special form of renal cystic disorder characterized by Bowman’s space dilatation in the absence of tubular cysts. ZEB2 is a SMAD-interacting transcription factor involved in Mowat-Wilson syndrome, a congenital disorder with an increased risk for kidney anomalies. Here we show that deletion of Zeb2in mesenchyme-derived nephrons with either Pax2-creor Six2-crecauses primary glomerulocystic kidney disease without tubular cysts in mice. Glomerulotubular junction analysis revealed many atubular glomeruli in the kidneys of Zeb2knockout mice, which explains the presence of glomerular cysts in the absence of tubular dilatation. Gene expression analysis showed decreased expression of early proximal tubular markers in the kidneys of Zeb2knockout mice preceding glomerular cyst formation, suggesting that defects in proximal tubule development during early nephrogenesis contribute to the formation of congenital atubular glomeruli. At the molecular level, Zeb2deletion caused aberrant expression of Pkd1, Hnf1β,and Glis3, three genes causing glomerular cysts. Thus, Zeb2regulates the morphogenesis of mesenchyme-derived nephrons and is required for proximal tubule development and glomerulotubular junction formation. Our findings also suggest that ZEB2might be a novel disease gene in patients with primary glomerular cystic disease. |
| Databáze: |
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