Autosomal dominant polycystic kidney disease decreases anion exchanger activity.
Autosomal dominant polycystic kidney disease decreases anion exchanger activity.
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常染色体显性多囊肾病会降低阴离子交换活性。
DOI：
10.1152/ajpcell.1997.272.5.c1748
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Jefferson,DM
中科院分区：
文献类型：
--
作者：
Perrone,RD;Grubman,SA;Murray,SL;Lee,DW;Alper,SL;Jefferson,DM
肝囊肿是常染色体显性遗传性多囊肾病（ADPKD）最常见的肾外表现，来源于肝内胆管上皮（IBE），在60-75%的ADPKD透析患者中发现。促胰液素诱导的正常IBE分泌富含HCO 3-，而完整的ADPKD肝囊肿主要分泌Cl-以响应促胰液素。为了评估ADPKD肝囊肿减少HCO 3-分泌的机制，我们利用我们创建的SV 40大T抗原永生化的正常IBE和ADPKD肝囊肿衍生上皮细胞（LCDE）细胞系。这些细胞系表达胆汁标志物，但不表达肝细胞标志物。通过细胞内pH（pHi）对急性Cl-去除的反应来评估阴离子交换（AE）功能。用含有Cl-或葡萄糖酸盐的生理HCO_3缓冲液连续灌注2 ′，7 ′-双（羧乙基）-5-（6）-羧基荧光素负载的单层。在IBE细胞系H75（n = 6）中，急性Cl-去除以0.04 +/- 0.01 min-1的速率碱化pHi。在LCDE细胞系CL 3（n = 6）中，Cl-去除后AE功能显著降低至0.01 +/- 0.01 min-1。北方印迹分析表明两种细胞系中AE 2 mRNA水平相等。AE 1 mRNA检测不到。免疫印迹分析表明AE 2多肽在两种细胞系中，但成熟的糖基化AE 2多肽的水平在LCDE细胞中降低。免疫荧光显微镜显示LCDE细胞膜定位AE 2减少。这些结果表明，质膜AE 2的减少可能是LCDE细胞AE功能降低的原因，并可能解释了ADPKD肝囊肿HCO 3-分泌减少的原因。
Liver cysts, the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD), derive from the intrahepatic biliary epithelium (IBE) and are found in 60-75% of ADPKD patients on dialysis. Secretin-induced secretion by the normal IBE is rich in HCO3-, whereas intact ADPKD liver cysts secrete primarily Cl- in response to secretin. To evaluate the mechanisms of decreased HCO3- secretion by ADPKD liver cysts, we utilized SV40 large T antigen-immortalized normal IBE and ADPKD liver cyst-derived epithelia (LCDE) cell lines that we created. These cell lines express biliary but not hepatocyte markers. Anion exchanger (AE) function was assessed by the response of intracellular pH (pHi) to acute Cl- removal. 2',7'-Bis(carboxyethyl)-5-(6)-carboxyfluorescein-loaded monolayers were continuously perfused with physiological HCO3- buffer containing Cl- or gluconate. In IBE cell line H75 (n = 6), acute Cl- removal alkalinized pHi at a rate of 0.04 +/- 0.01 min-1. AE function was significantly decreased in LCDE cell line CL3 (n = 6) to a rate of 0.01 +/- 0.01 min-1 after Cl- removal. Northern blot analysis demonstrated equivalent levels of AE2 mRNA in both cell lines. AE1 mRNA was undetectable. Immunoblot analysis demonstrated the AE2 polypeptide in both cell lines, but the level of mature glycosylated AE2 polypeptide was reduced in LCDE cells. Immunofluorescence microscopy demonstrated decreased membrane-localized AE2 in LCDE cells. These findings suggest that decreased plasmalemmal AE2 may account for decreased AE function in LCDE cells and suggest a possible explanation for decreased secretion of HCO3- by ADPKD liver cysts.
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影响因子：
19.6
作者：
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通讯作者：
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DOI：
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作者：
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DOI：
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发表时间：
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影响因子：
11.1
作者：
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影响因子：
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作者：
A. M. Waitman;W. Dyck;H. Janowitz
通讯作者：
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