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| 1 | The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia显示文摘Tumor-induced osteomalacia(TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23(FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1α(HIF-1α) in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-1α mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-1α and FGF23 were co-localized in spindleshaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-1α protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-1α expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-1α inhibitors decreased HIF-1α and FGF23 protein accumulation and inhibited HIF-1α-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-1α consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-1α inhibitor. These results show for the first time that HIF-1α is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-1α activity in TIO contributes to the aberrant FGF23 production in these patients. | Qian Zhang Michele Doucet Ryan E Tomlinson Xiaobin Han L Darryl Quarles Michael T Collins Thomas L Clemens | 2016 | Bone Research2016，4，2： | 6 |
| 2 | Tolerance to toxic metals by a gene family of phytochelatin synthases from plants and yeast显示文摘 | CLEMENS S KIM E J NEUMANN D | 1999 | EMBO J1999，18，： | 1 |
| 3 | Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care显示文摘 | Katharine Bushby Richard Finkel David J Birnkrant Laura E Case Paula R Clemens Linda Cripe Ajay Kaul Kathi Kinnett Craig McDonald Shree Pandya James Poysky Frederic Shapiro Jean Tomezsko Carolyn Constantin | 2010 | Lancet Neurology2010，，2： | 1 |
| 4 | Dyspnoea associated with anxiety-symptomatic therapy with opioids in combination with lorazepam and its effect on ventilation in palliative care patients 显示文摘 | Clemens KE Klaschik E | 2011 | Support Care Cancer2011，19，12： | 1 |
| 5 | On the structure and origin of major glaciation cycles,1:Linear responses to Milankovitch forcing显示文摘 | IMBRIE J BOYLE E CLEMENS S | 1992 | Paleoceanography1992，7，： | 1 |
| 6 | Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices显示文摘 | Hansen K J Clemen L A Ellefson M E | 2001 | Environ Sci Technol2001，35，4： | 1 |
| 7 | The Impact Of Guideline Compliant Medical Therapy on ebinial Outcome in Patients With Stable Angina: Findings from the Eur Heat Survey of Stable Angina显示文摘 | Daly e Clemens F Lopez-Sendon JL | 2006 | Eur Heat J2006，27，11： | 1 |
| 8 | Local administration of IL-12-transfected dendritic cells induces antitumor immune responses to colon adenocarcinoma in the liver in mice显示文摘 | Yuji S Clemens E Andrea G | 1998 | J Exp Ther And Oncol1998，2，5： | 1 |
| 9 | Tolerance to toxic metals by a gene family of phytochelatin synthases from plants and yeast显示文摘 | Clemens S Kim E J Neumann D | | 0，，12： | 1 |
| 10 | Tolerance to toxic metals by a gene family of phytochelatin synthases from plants and yeast显示文摘 | CLEMENS S KIM E J NEUMANN D | 1999 | The EMBO Journal1999，18，12： | 1 |
| 11 | Global risk management in type 2 di- abetes: blood glucose, blood pressure, and lipids--update on the background of the current guidelines显示文摘 | Clemens A Siegel E Gallwitz B | 2004 | Exp Clin Endocrinol Diabe- tes2004，112，9： | 1 |
| 12 | Tolerance to toxic metals by a gene family of phytochelatin synthases from plants and yeast显示文摘 | Clemens S Kim E J Neumann D | 1999 | E1VI]3() Journal1999，，18： | 1 |
| 13 | The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development显示文摘 | Wang Y Wan C Deng L Liu X Cao X Gilbert SR Bouxsein ML Faugere M-C Guldberg RE Gerstenfeld LC Haase VH Johnson RS Schipani E Clemens TL | | 0，，： | 1 |
| 14 | The impact of guideline compliant Medical Therapy on cbinial Outcom in Patiens with Stabl Angina:Fings from the Eur Heart Survey of Stable Angina显示文摘 | Daly E Clemens F Lopez-send JL | 2006 | Eur Heart J2006，27，11： | 1 |
| 15 | The impact of guideline compliant medical therapy on clinical outcome in patients with stable angina:findings from the Eur Heat Survey of stable angina显示文摘 | Daly E Clemens F Lopez-sendon JL | | 0，，11： | 1 |
| 16 | The artificial beta cell-a continuous control of blood sugar by external regulation of insulin 显示文摘 | Pfeiffer E F Thum C Clemens A H | 1974 | Horm Metab Res1974，487，： | 1 |
| 17 | On the structure and origin of major glaciation cycles, 1, Linear responses to Milankovitch forcing 显示文摘 | Imbrie J Boyle E Clemens S | 1992 | Paleoceanography1992，7，： | 1 |
| 18 | Per-formance evaluation of texture measures for ground coveridentification in satellite images by means of a neural net-work classifier 显示文摘 | AUGUSTEUN M F CLEMENS L E SHAW K A | 1995 | IEEE Transactions on Geoscienceand Remote Sensing1995，33，3： | 1 |
| 19 | Compound-specific,quantitative characterization of organic fluorochemicals in biological matrices显示文摘 | Hansen K J Clemen L A Ellefson M E | 2001 | Environ Sci Technol2001，35，： | 1 |
| 20 | The two transcription units of the autonomous parvovirus minute virus of mice are transcribed in a temporal order显示文摘 | CLEMENS K E PINTEL D J | 1988 | J Virol1988，62，： | 1 |
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