The systems biology of uric acid transporters: the role of remote sensing and signaling.
The systems biology of uric acid transporters: the role of remote sensing and signaling.
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DOI：
10.1097/mnh.0000000000000427
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发表时间：
2018-07
影响因子：
3.2
通讯作者：
Bhatnagar V
中科院分区：
文献类型：
--
作者：
Nigam SK;Bhatnagar V
体内尿酸稳态由肾脏和肠中的许多SLC和ABC转运蛋白介导，包括几种多特异性“药物”转运蛋白（例如，OAT 1、OAT 3和ABCG 2）。尿酸水平的优化可以被视为一个“系统生物学”问题。在这里，我们认为尿酸转运蛋白从系统生理学的角度来看，使用的框架“遥感和信号假说”。这一假说解释了SLC和ABC“药物”和其他转运蛋白如何介导器官间和生物体间的通讯（例如，肠道微生物组和宿主）通过小分子（例如，代谢物，抗氧化剂信号分子）通过在衬于体液隔室的组织中表达的转运蛋白（例如，血液、尿液、脑脊髓液）。尿酸转运蛋白列表包括：SLC 2A 9、ABCG 2、URAT 1（SLC 22 A12）、OAT 1（SLC 22 A6）、OAT 3（SLC 22 A8）、OAT 4（SLC 22 A11）、OAT 10（SLC 22 A13）、NPT 1（SLC 17 A1）、NPT 4（SLC 17 A3）、MRP 2（ABCC 2）、MRP 4（ABCC 4）。通常，SLC 2A 9-沿着URAT 1、OAT 1和OAT 3-似乎是调节肾脏尿酸盐处理的主要转运蛋白，而ABCG 2似乎调节肠道转运。在慢性肾病（CKD）中，肠道ABCG 2变得更加重要，这表明受损肾脏和肠道之间存在远程器官通讯。遥感和信号传导假说提供了一个有用的系统水平框架，用于理解在正常和患病条件下参与优化尿酸水平的不同组织中表达的尿酸转运蛋白的复杂相互作用（例如，CKD，肠道微生物菌群失调）状况。
Uric acid homeostasis in the body is mediated by a number of SLC and ABC transporters in the kidney and intestine, including several multispecific ‘drug’ transporters (e.g., OAT1, OAT3, and ABCG2). Optimization of uric acid levels can be viewed as a ‘systems biology’ problem. Here, we consider uric acid transporters from a systems physiology perspective using the framework of the ‘Remote Sensing and Signaling Hypothesis.’ This hypothesis explains how SLC and ABC ‘drug’ and other transporters mediate interorgan and interorganismal communication (e.g., gut microbiome and host) via small molecules (e.g., metabolites, antioxidants signaling molecules) through transporters expressed in tissues lining body fluid compartments (e.g., blood, urine, cerebrospinal fluid). The list of uric acid transporters includes: SLC2A9, ABCG2, URAT1 (SLC22A12), OAT1 (SLC22A6), OAT3 (SLC22A8), OAT4 (SLC22A11), OAT10 (SLC22A13), NPT1 (SLC17A1), NPT4 (SLC17A3), MRP2 (ABCC2), MRP4 (ABCC4). Normally, SLC2A9, – along with URAT1, OAT1 and OAT3, – appear to be the main transporters regulating renal urate handling, while ABCG2 appears to regulate intestinal transport. In chronic kidney disease (CKD), intestinal ABCG2 becomes much more important, suggesting remote organ communication between the injured kidney and the intestine. The remote sensing and signaling hypothesis provides a useful systems-level framework for understanding the complex interplay of uric acid transporters expressed in different tissues involved in optimizing uric acid levels under normal and diseased (e.g., CKD, gut microflora dysbiosis) conditions.