Renal injury is a third hit promoting rapid development of adult polycystic kidney disease
Renal injury is a third hit promoting rapid development of adult polycystic kidney disease
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DOI：
10.1093/hmg/ddp147
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发表时间：
2009-07-15
影响因子：
3.5
通讯作者：
Zhou, Jing
中科院分区：
文献类型：
--
作者：
Takakura, Ayumi;Contrino, Leah;Zhou, Jing
常染色体显性多囊肾病进行性囊肿形成的“双击”模式是一种被广泛接受的遗传机制。我们之前已经证明，使用Mx1Cre（+）等位基因的成人Pkd1失活导致局灶性囊性疾病的晚发性。对囊肿延迟出现的一种解释是需要额外的独立因素，或“第三次打击”。本研究表明，在同一小鼠系中，肾脏损伤可导致大量囊性疾病。囊肿用收集管/小管标记物凝集素（Lectin Dolichos biflorus Agglutinin）标记，这与收集系统中cre介导的重组位点有关。5-溴-2'-脱氧尿苷标记表明，囊壁上皮细胞是由肾损伤后的再生细胞组成的。这些数据首次证明了多囊素-1在肾损伤和修复中的作用，并表明肾损伤是导致成年期快速囊肿形成的“第三次打击”。
The 'two-hit' model is a widely accepted genetic mechanism for progressive cyst formation in autosomal dominant polycystic kidney disease. We have previously shown that adult inactivation of Pkd1 using the Mx1Cre(+) allele causes a late onset of focal cystic disease. An explanation for the delayed appearance of cysts is the requirement for an additional independent factor, or 'third hit'. Here we show that renal injury leads to massive cystic disease in the same mouse line. Cysts are labeled with a collecting duct/tubule marker, Lectin Dolichos biflorus Agglutinin, which correlates with the site of Cre-mediated recombination in the collecting system. 5-Bromo-2'-deoxyuridine labeling reveals that cyst-lining epithelial cells are comprised of regenerated cells in response to renal injury. These data demonstrate, for the first time, a role for polycystin-1 in kidney injury and repair and indicate that renal injury constitutes a 'third hit' resulting in rapid cyst formation in adulthood.