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The systems biology of uric acid transporters: the role of remote sensing and signaling

Nigam, Sanjay, K.a; Bhatnagar, Vibhab

Current Opinion in Nephrology and Hypertension: July 2018 - Volume 27 - Issue 4 - p 305–313
doi: 10.1097/MNH.0000000000000427
RENAL PATHOPHYSIOLOGY: Edited by Orson W. Moe and Susan Quaggin
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Purpose of review 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).

Recent findings 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.

Summary 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.

aDepartments of Pediatrics and Medicine

bDepartment of Family Medicine and Public Health, University of California San Diego, La Jolla, Califonia, USA

Correspondence to Sanjay K. Nigam, Department of Pediatrics and Medicine, University of California San Diego, 9500 Gilman Drive, MC0693, La Jolla, CA 92093. USA. E-mail: snigam@ucsd.edu

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