Jiang Zhirong, Asplin John R, Evan Andrew P, Rajendran Vazhaikkurichi M, Velazquez Heino, Nottoli Timothy P, Binder Henry J, Aronson Peter S
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nat Genet. 2006 Apr;38(4):474-8. doi: 10.1038/ng1762. Epub 2006 Mar 12.
Urolithiasis is one of the most common urologic diseases in industrialized societies. Calcium oxalate is the predominant component in 70-80% of kidney stones, and small changes in urinary oxalate concentration affect the risk of stone formation. SLC26A6 is an anion exchanger expressed on the apical membrane in many epithelial tissues, including kidney and intestine. Among its transport activities, SLC26A6 mediates Cl(-)-oxalate exchange. Here we show that mutant mice lacking Slc26a6 develop a high incidence of calcium oxalate urolithiasis. Slc26a6-null mice have significant hyperoxaluria and elevation in plasma oxalate concentration that is greatly attenuated by dietary oxalate restriction. In vitro flux studies indicated that mice lacking Slc26a6 have a defect in intestinal oxalate secretion resulting in enhanced net absorption of oxalate. We conclude that the anion exchanger SLC26A6 has a major constitutive role in limiting net intestinal absorption of oxalate, thereby preventing hyperoxaluria and calcium oxalate urolithiasis.
尿石症是工业化社会中最常见的泌尿系统疾病之一。草酸钙是70%-80%肾结石的主要成分，尿草酸浓度的微小变化会影响结石形成的风险。SLC26A6是一种阴离子交换体，在包括肾脏和肠道在内的许多上皮组织的顶端膜上表达。在其转运活动中，SLC26A6介导Cl(-)-草酸交换。在此我们表明，缺乏Slc26a6的突变小鼠患草酸钙尿石症的发生率很高。Slc26a6基因敲除小鼠有明显的高草酸尿症，血浆草酸浓度升高，而饮食中限制草酸摄入可大大减轻这种情况。体外通量研究表明，缺乏Slc26a6的小鼠肠道草酸分泌存在缺陷，导致草酸净吸收增加。我们得出结论，阴离子交换体SLC26A6在限制肠道草酸净吸收方面起主要的组成性作用，从而预防高草酸尿症和草酸钙尿石症。
