Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease.
Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease.
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DOI：
10.1016/j.kint.2016.06.037
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发表时间：
2016-12
影响因子：
19.6
通讯作者：
Lu, Weining
中科院分区：
文献类型：
--
作者：
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
原发性肾小球囊性肾病是一种特殊形式的肾脏囊性疾病，其特征是在没有管状囊肿的情况下Bowman空间扩张。ZEB 2是一种SMAD相互作用转录因子，与Mowat-Wilson综合征有关，Mowat-Wilson综合征是一种先天性疾病，肾脏异常风险增加。在这里，我们表明，Zeb 2在间充质来源的肾单位与Pax 2-cre或Six 2-cre的缺失导致原发性肾小球囊性肾病没有管状囊肿的小鼠。肾小球管连接分析显示，在Zeb 2基因敲除小鼠的肾脏中存在许多无小管肾小球，这解释了在没有肾小管扩张的情况下存在肾小球囊肿。基因表达分析显示，在肾小球囊肿形成之前，Zeb 2基因敲除小鼠肾脏中早期近端小管标记物的表达降低，表明早期肾发生过程中近端小管发育的缺陷有助于先天性无小管肾小球的形成。在分子水平上，Zeb 2基因缺失导致Pkd 1、Hnf 1 β和Glis 3基因的异常表达，这三个基因导致肾小球囊肿。因此，Zeb 2调节间充质来源的肾单位的形态发生，并且是近端小管发育和肾小球管连接形成所需的。我们的研究结果还表明，ZEB 2可能是一个新的疾病基因在原发性肾小球囊性疾病患者。
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 Zeb2 in mesenchyme-derived nephrons with either Pax2-cre or Six2-cre causes primary glomerulocystic kidney disease without tubular cysts in mice. Glomerulotubular junction analysis revealed many atubular glomeruli in the kidneys of Zeb2 knockout 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 Zeb2 knockout 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, Zeb2 deletion caused aberrant expression of Pkd1, Hnf1β, and Glis3, three genes causing glomerular cysts. Thus, Zeb2 regulates the morphogenesis of mesenchyme-derived nephrons and is required for proximal tubule development and glomerulotubular junction formation. Our findings also suggest that ZEB2 might be a novel disease gene in patients with primary glomerular cystic disease.
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影响因子：
3.5
作者：
El-Kasti, Muna M.;Wells, Timothy;Carter, David A.
通讯作者：
Carter, David A.
影响因子：
2.6
作者：
Ho J
通讯作者：
Ho J
DOI：
10.1073/pnas.0605266104
发表时间：
2007-01-30
影响因子：
11.1
作者：
Hossain, Zakir;Ali, Safiah Mohamed;Hunziker, Walter
通讯作者：
Hunziker, Walter
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
影响因子：
3.3
作者：
Gregory PA;Bracken CP;Smith E;Bert AG;Wright JA;Roslan S;Morris M;Wyatt L;Farshid G;Lim YY;Lindeman GJ;Shannon MF;Drew PA;Khew-Goodall Y;Goodall GJ
通讯作者：
Goodall GJ