Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김원동 | - |
dc.date.accessioned | 2021-07-22T05:26:35Z | - |
dc.date.available | 2021-07-22T05:26:35Z | - |
dc.date.issued | 2020-03 | - |
dc.identifier.citation | JOURNAL OF CLINICAL INVESTIGATION,v. 130, no. 3, page. 1513-1526 | en_US |
dc.identifier.issn | 1558-8238 | - |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | https://www.proquest.com/docview/2383820325?accountid=11283 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/163091 | - |
dc.description.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. | en_US |
dc.description.sponsorship | This work was supported by NIH grants R01-NR-017399 and U01- DK-106981 (to EPR); K08-AR-067285 and R01-DK-116716 (to MNW); P01-DK011794 (subproject 3, to HJ); R01-AR-067291 (to WC); and R01-HL-133870, R01-HL-132320, and R01-DK-081572 ( to REG); and by a grant from the Extramural Grant Program of Satellite Healthcare, a not-for-profit renal care provider (to EPR). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | American Society for Clinical Investigation INC | en_US |
dc.title | Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1172/JCI131190 | - |
dc.relation.page | 1513-1526 | - |
dc.relation.journal | JOURNAL OF CLINICAL INVESTIGATION | - |
dc.contributor.googleauthor | Simic, P. | - |
dc.contributor.googleauthor | Kim, W. | - |
dc.contributor.googleauthor | Zhou, W. | - |
dc.contributor.googleauthor | Thadhani, R. | - |
dc.contributor.googleauthor | Rhee, E.P. | - |
dc.contributor.googleauthor | Govea, N. | - |
dc.contributor.googleauthor | Jüppner, H. | - |
dc.contributor.googleauthor | Wein, M.N. | - |
dc.contributor.googleauthor | Pierce, K.A. | - |
dc.contributor.googleauthor | Gerszten, R.E. | - |
dc.relation.code | 2020049426 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF PHARMACY[E] | - |
dc.sector.department | DEPARTMENT OF PHARMACY | - |
dc.identifier.pid | wdongkim | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.