Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice
Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice
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DOI：
10.1172/jci31474
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发表时间：
2010-03-01
影响因子：
15.9
通讯作者：
Markovich, Daniel
中科院分区：
文献类型：
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作者：
Dawson, Paul A.;Russell, Christopher S.;Markovich, Daniel
尿石症是一种结石存在于泌尿系统（包括肾脏和膀胱）中的疾病，是一种世界范围内知之甚少但常见的疾病，导致显著的医疗保健成本，发病率和工作损失。对乙酰氨基酚引起的肝损伤是急性肝功能衰竭患者死亡的主要原因。肾和泌尿系统结石以及肝毒性分别是与草酸盐和硫酸盐稳态改变相关的紊乱。硫酸盐阴离子转运蛋白-1（Sat1;也称为Slc26a1）介导草酸盐和硫酸盐的上皮转运，其在肾脏、肝脏和肠中的定位表明其可能在草酸盐和硫酸盐稳态中发挥作用。为了确定Sat1的生理作用，我们通过基因破坏创建了Sat1（-/-）小鼠。这些小鼠表现出高尿症。高尿酸血症、肾钙质沉着症、肾小管及膀胱草酸钙结石。Sat1（-/-）小鼠还表现出高硫酸盐尿症、低硫酸盐血症和增强的对乙酰氨基酚诱导的肝毒性。这些数据表明，Sat1调节草酸盐和硫酸盐稳态，可能是草酸钙尿石症和肝毒性的发展至关重要。
Urolithiasis, a condition in which stones are present in the urinary system, including the kidneys and bladder, is a poorly understood yet common disorder worldwide that leads to significant health care costs, morbidity, and work loss. Acetaminophen-induced liver damage is a major cause of death in patients with acute liver failure. Kidney and urinary stones and liver toxicity are disturbances linked to alterations in oxalate and sulfate homeostasis, respectively. The sulfate anion transporter-1 (Sat1; also known as Slc26a1) mediates epithelial transport of oxalate and sulfate, and its localization in the kidney, liver, and intestine suggests that it may play a role in oxalate and sulfate homeostasis. To determine the physiological roles of Sat1, we created Sat1(-/-) mice by gene disruption. These mice exhibited hyperoxaluria. with hyperoxalemia, nephrocalcinosis, and calcium oxalate stones in their renal tubules and bladder. Sat1(-/-) mice also displayed hypersulfaturia, hyposulfatemia, and enhanced acetaminophen-induced liver toxicity. These data suggest that Sat1 regulates both oxalate and sulfate homeostasis and may be critical to the development of calcium oxalate urolithiasis and hepatotoxicity.