Department of Medicine, University of California, San Francisco, CA 94158, USA.
Development. 2011 May;138(10):2099-109. doi: 10.1242/dev.056564.
Defects in the development or maintenance of tubule diameter correlate with polycystic kidney disease. Here, we report that absence of the cadherin regulator p120 catenin (p120ctn) from the renal mesenchyme prior to tubule formation leads to decreased cadherin levels with abnormal morphologies of early tubule structures and developing glomeruli. In addition, mutant mice develop cystic kidney disease, with markedly increased tubule diameter and cellular proliferation, and detached luminal cells only in proximal tubules. The p120ctn homolog Arvcf is specifically absent from embryonic proximal tubules, consistent with the specificity of the proximal tubular phenotype. p120ctn knockdown in renal epithelial cells in 3D culture results in a similar cystic phenotype with reduced levels of E-cadherin and active RhoA. We find that E-cadherin knockdown, but not RhoA inhibition, phenocopies p120ctn knockdown. Taken together, our data show that p120ctn is required for early tubule and glomerular morphogenesis, as well as control of luminal diameter, probably through regulation of cadherins.
在管状直径的发育或维持过程中的缺陷与多囊肾病相关。在这里，我们报告说，在肾小管形成之前，p120 连环蛋白（p120ctn）从肾间质中缺失会导致钙粘蛋白水平降低，早期肾小管结构和发育中的肾小球形态异常。此外，突变小鼠会发展为囊性肾病，肾小管直径明显增大，细胞增殖增加，只有近端小管的腔细胞分离。p120ctn 同源物 Arvcf 特异性缺失于胚胎近端小管中，与近端小管表型的特异性一致。在 3D 培养的肾上皮细胞中敲低 p120ctn 会导致类似的囊性表型，E-钙粘蛋白水平降低，活性 RhoA 增加。我们发现，E-钙粘蛋白敲低而非 RhoA 抑制可模拟 p120ctn 敲低。总之，我们的数据表明，p120ctn 对于早期肾小管和肾小球形态发生以及管腔直径的控制是必需的，可能通过调节钙粘蛋白来实现。
