{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:54:20Z","timestamp":1792637660034,"version":"4.5.0"},"reference-count":36,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:p>Fibroblast growth factor-23 (FGF-23) is critical to the pathogenesis of a distinct group of renal phosphate wasting disorders: tumor-induced osteomalacia, X-linked hypophosphatemia, and autosomal dominant and autosomal recessive hypophosphatemic rickets. Excess circulating FGF-23 is responsible for their major phenotypic features which include hypophosphatemia due to renal phosphate wasting and inappropriately low serum 1,25(OH)<jats:sub>2<\/jats:sub>D concentrations. To characterize the effects of FGF-23 on renal sodium-phosphate (Na\/P<jats:sub>i<\/jats:sub>) cotransport and vitamin D metabolism, we administered FGF-23(R176Q) to normal mice. A single injection (0.33 \u03bcg\/g body wt) induced significant hypophosphatemia, 20 and 29% decreases ( P &lt; 0.001) in brush-border membrane (BBM) Na\/P<jats:sub>i<\/jats:sub>cotransport at 5 and 17 h after injection, respectively, and comparable decreases in the abundance of type IIa Na\/P<jats:sub>i<\/jats:sub>cotransporter protein in BBM. Multiple injections (6, 12, and 24 \u03bcg\/day for 4 days) induced dose-dependent decreases (38, 63, and 75%, respectively) in renal abundance of 1\u03b1-hydroxylase mRNA ( P &lt; 0.05). To determine whether FGF-23(R176Q) exerts a direct action on 1\u03b1-hydroxylase gene expression, we examined its effects in cultured human (HKC-8) and mouse (MCT) renal proximal tubule cells. FGF-23(R176Q) (1 to 10 ng\/ml) induced a dose-dependent decrease in 1\u03b1-hydroxylase mRNA with a maximum suppression of 37% ( P &lt; 0.05). Suppression was detectable after 6 h of exposure and maximal after 21 h. In MCT cells, FGF-23(R176Q) suppressed 1\u03b1-hydroxylase mRNA and activated the ERK1\/2 signaling pathway. The MAPK inhibitor PD98059 effectively abolished FGF-23-induced suppression of 1\u03b1-hydroxylase mRNA by blocking signal transduction via ERK1\/2. These novel findings provide evidence that FGF-23 directly regulates renal 1\u03b1-hydroxylase gene expression via activation of the ERK1\/2 signaling pathway.<\/jats:p>","DOI":"10.1152\/ajprenal.00463.2006","type":"journal-article","created":{"date-parts":[[2007,8,16]],"date-time":"2007-08-16T00:15:08Z","timestamp":1187223308000},"page":"F1577-F1583","source":"Crossref","is-referenced-by-count":260,"title":["Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1\u03b1-hydroxylase expression in vitro"],"prefix":"10.1152","volume":"293","author":[{"given":"Farzana","family":"Perwad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Y. H.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet S.","family":"Tenenhouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony A.","family":"Portale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210490200"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.5.6683"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1038\/276287a0"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1038\/ng1905"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1038\/228764a0"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1126\/science.172.3989.1232"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Gray RW, Omdahl JL, Ghazarian JG, DeLuca HF.25-Hydroxycholecalciferol-1\u03b1-hydroxylase.J Biol Chem247: 7528\u20137532, 1972.","DOI":"10.1016\/S0021-9258(19)44557-2"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-39-6-1045"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.4.1359"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7103"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.03.090"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020881"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.2009"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.2.1199"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(00)00065-9"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.2741\/Klint"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500457200"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112766"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1768"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1247\/csf.29.91"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1038\/ng1868"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9098"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Paulson SK, DeLuca HF.Subcellular location and properties of rat renal 25-hydroxyvitamin D3-1\u03b1-hydroxylase.J Biol Chem260: 11488\u201311492, 1985.","DOI":"10.1016\/S0021-9258(17)39055-5"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0777"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1677\/erc.0.0070165"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(97)90180-3"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105396"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.0301264"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.101545198"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.8.8795"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)60149-7"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117019"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1038\/81664"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1038\/nature05315"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202527200"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0670"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00463.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T21:26:58Z","timestamp":1629581218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00463.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2007,11]]}},"alternative-id":["10.1152\/ajprenal.00463.2006"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00463.2006","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11]]}}}