Structural and functional analyses of liver cysts from the BALB/c-cpk mouse model of polycystic kidney disease.
Structural and functional analyses of liver cysts from the BALB/c-cpk mouse model of polycystic kidney disease.
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DOI：
10.3181/0807-rm-215
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Blazer-Yost BL
中科院分区：
文献类型：
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作者：
Muchatuta MN;Gattone VH 2nd;Witzmann FA;Blazer-Yost BL
肝胆管产生的肝囊肿是一种常见的肾外病理，与人类常染色体显性和隐性多囊肾病相关。为了阐明囊肿形成和生长所固有的功能和结构变化，从多囊肾病的 BALB/c-cpk 小鼠模型中分离出肝胆管上皮。光学和透射电子显微镜显示，从杂合子（BALB/c-cpk/+）和纯合子（BALB/c-cpk/cpk）动物中分离出的肝胆管囊肿周围的基底层中存在大量纤维化。对正常、囊前和囊性胆管的扫描电子显微镜和长度分析提供了独特的观察结果，即从表达突变cpk基因的动物的胆管和囊肿中分离出的胆管细胞中的初级纤毛的长度超出了野生型动物胆管内壁细胞的最小和最大范围。基于 PKD 是几种以纤毛病为特征的疾病之一的假设，初级纤毛长度的异常变异可能具有功能意义。对新鲜分离的囊肿的电生理分析表明，阿米洛利敏感的上皮 Na+ 通道 (ENaC) 不活跃/不存在，cAMP 介导的阴离子分泌是导致囊肿液积聚的生电转运过程。腺苷酸环化酶的管腔刺激可刺激阴离子分泌。
Liver cysts arising from hepatic bile ducts are a common extra-renal pathology associated with both autosomal dominant and recessive polycystic kidney disease in humans. To elucidate the functional and structural changes inherent in cyst formation and growth, hepatic bile duct epithelia were isolated from the BALB/c-cpk mouse model of polycystic kidney disease. Light and transmission electron microscopy revealed substantial fibrosis in the basal lamina surrounding hepatic bile duct cysts isolated from heterozygous (BALB/c-cpk/+) and homozygous (BALB/c-cpk/cpk) animals. Scanning electron microscopy and length analysis of normal, precystic and cystic bile ducts provided the unique observation that primary cilia in cholangiocytes isolated from bile ducts and cysts of animals expressing the mutated cpk gene had lengths outside the minimal and maximal ranges of those in cells lining bile ducts of wild-type animals. Based on the hypothesis that PKD is one of several diseases characterized as ciliopathies, this abnormal variability in the length of the primary cilia may have functional implications. Electrophysiological analyses of freshly isolated cysts indicate that the amiloride-sensitive epithelial Na+ channel (ENaC) is inactive/absent and cAMP-mediated anion secretion is the electrogenic transport process contributing to cyst fluid accumulation. Anion secretion can be stimulated by the luminal stimulation of adenylyl cyclase.