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Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney

Title
Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney
Author
김원동
Issue Date
2020-03
Publisher
American Society for Clinical Investigation INC
Citation
JOURNAL OF CLINICAL INVESTIGATION,v. 130, no. 3, page. 1513-1526
Abstract
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls blood phosphate levels by increasing renal phosphate excretion and reducing 1,25-dihydroxyvitamin D3 [1,25(OH)2D] production. Disorders of FGF23 homeostasis are associated with significant morbidity and mortality, but a fundamental understanding of what regulates FGF23 production is lacking. Because the kidney is the major end organ of FGF23 action, we hypothesized that it releases a factor that regulates FGF23 synthesis. Using aptamer-based proteomics and liquid chromatography–mass spectrometry–based (LC-MS–based) metabolomics, we profiled more than 1600 molecules in renal venous plasma obtained from human subjects. Renal vein glycerol-3-phosphate (G-3-P) had the strongest correlation with circulating FGF23. In mice, exogenous G-3-P stimulated bone and bone marrow FGF23 production through local G-3-P acyltransferase–mediated (GPAT-mediated) lysophosphatidic acid (LPA) synthesis. Further, the stimulatory effect of G-3-P and LPA on FGF23 required LPA receptor 1 (LPAR1). Acute kidney injury (AKI), which increases FGF23 levels, rapidly increased circulating G-3-P in humans and mice, and the effect of AKI on FGF23 was abrogated by GPAT inhibition or Lpar1 deletion. Together, our findings establish a role for kidney-derived G-3-P in mineral metabolism and outline potential targets to modulate FGF23 production during kidney injury.
URI
https://www.proquest.com/docview/2383820325?accountid=11283https://repository.hanyang.ac.kr/handle/20.500.11754/163091
ISSN
1558-8238; 0021-9738
DOI
10.1172/JCI131190
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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