The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man.
The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man.
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DOI：
10.1007/s00240-016-0952-z
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发表时间：
2017-02
期刊：
影响因子：
3.1
通讯作者：
Hatch M
中科院分区：
文献类型：
--
作者：
Whittamore JM;Hatch M
肠道通过两种方式对尿草酸产生相当大的影响，一种是通过吸收饮食中的草酸，另一种是作为一种适应性的肾外途径来消除这种废物代谢物。因此，了解肠道吸收和分泌草酸的机制对于了解高草酸尿症的病因以及为草酸钙肾结石的未来治疗策略提供潜在的靶点具有重要意义。在这篇综述中，我们介绍了过去10年来这一领域的最新发展和进展，并利用人和小鼠模型检验了在此期间出现的一些新想法。我们讨论的一个关键焦点是膜结合的阴离子交换器，属于SLC26基因家族，其中一些已被证明参与跨细胞草酸的吸收和分泌。这不仅为研究这些特定转运蛋白的作用提供了机会，揭示了它们对草酸稳态的重要性，还提供了探索草酸跨细胞和被动细胞旁成分跨肠道运输的相对贡献的机会。我们还讨论了一些不同的生理刺激和信号通路，它们被认为参与了肠道草酸运输的适应和调节。最后，我们提供了对草酸杆菌形成菌的研究的最新情况，以及最近在实验室动物和人类中对其他降解草酸的肠道细菌的研究。
The intestine exerts a considerable influence over urinary oxalate in two ways, through the absorption of dietary oxalate and by serving as an adaptive extra-renal pathway for elimination of this waste metabolite. Knowledge of the mechanisms responsible for oxalate absorption and secretion by the intestine therefore have significant implications for understanding the etiology of hyperoxaluria, as well as offering potential targets for future treatment strategies for calcium oxalate kidney stone disease. In this review, we present the recent developments and advances in this area over the past 10 years, and put to the test some of the new ideas that have emerged during this time, using human and mouse models. A key focus for our discussion are the membrane-bound anion exchangers, belonging to the SLC26 gene family, some of which have been shown to participate in transcellular oxalate absorption and secretion. This has offered the opportunity to not only examine the roles of these specific transporters, revealing their importance to oxalate homeostasis, but to also probe the relative contributions made by the active transcellular and passive paracellular components of oxalate transport across the intestine. We also discuss some of the various physiological stimuli and signaling pathways which have been suggested to participate in the adaptation and regulation of intestinal oxalate transport. Finally, we offer an update on research into Oxalobacter formigenes, alongside recent investigations of other oxalate-degrading gut bacteria, in both laboratory animals and humans.