bFGF/FGFR1信号传递与心血管疾病关系的研究进展

碱性成纤维细胞生长因子 (b FGF)作为一种强的血管源性生长因子与心血管疾病的发生、发展有着密切的关系。介绍了 b FGF/ FGFR1的信号传递及其与心血管疾病的关系和在心肌缺血和增生性疾病中的治疗作用     

FGF23、MEPE和sFRP4在肿瘤性骨软化症发病机制中的作用

目的 探讨成纤维细胞生长因子-23（FGF-23）、细胞外基质磷酸糖蛋白（MEPE）和分泌型卷曲相关蛋白（sFRP4）在肿瘤性骨软化症（TIO）发病机制中的作用。方法 TIO肿瘤8例（T1-T8），其他间叶肿瘤5例（C1-C5），低血磷骨软化症病人行股骨手术，病理为凝血坏死组织1例（P1），正常人骨骼、肌肉组织各2例（B1、B2、M1和M2）。RT-PCR检测组织中FGF23、MEPE、sFRP4 mRNA的表达，Western blot检测TIO肿瘤FGF23蛋白的表达。TIO 4例（T1、T3、T4和T7）及P1在手术前后分别取血测定血清磷和FGF23（ELISA）水平。结果 TIO肿瘤有数量不等的FGF23和MEPE的mRNA表达，部分肿瘤表达sFRP4的mRNA。7/8例TIO肿瘤有不同强度FGF23蛋白表达。TIO术前血FGF23升高，术后2～24h降至正常；血磷3～10d缓慢升至正常， P1病人术后血FGF23无变化，血磷未上升。FGF23与MEPE mRNA正相关（r＝0.884，P＜0.05），FGF23 mRNA与蛋白表达之间成正相关关系（r＝0.921，P＜0.05）。结论 FGF23是TIO发病的主要原因，MEPE在TIO肿瘤发病中起到一定作用，sFRP4的作用尚不明确。     

血清CTRP9、 TNFR1、 FGF23与2型糖尿病患者下肢动脉血管病变的相关性研究

目的 探讨2型糖尿病(T2DM)患者血清C1q/肿瘤坏死因子相关蛋白9(CTRP9)、肿瘤坏死因子受体1(TNFR1)、成纤维细胞生长因子23 (FGF23)表达水平,分析其与患者下肢动脉血管病变(LEAD)的关系.方法 选取2018年1月至2020年1月在我院接收治疗的T2DM患者142例(病例组),根据踝臂指数(ABI),将其分为单纯T2DM组(ABI＞0.90,n=95)和合并LEAD组(ABI≤0.90,n=47).另选取我院体检健康人群100例(观察组).采用酶联免疫吸附法检测血清CTRP9、TNFR1、FGF23表达水平.应用Pearson相关性分析血清CTRP9、TNFR1、FGF23水平与LEAD的相关性.绘制ROC曲线,分析血清CTRP9、TNFR1、FGF23对T2DM患者LEAD发生的预测价值.结果 病例组血清CTRP9、TNFR1、FGF23水平与对照组相比,差异有统计学意义(P＜0.05).LEAD组血清CTRP9水平低于单纯T2DM组,血清TNFR1、FGF23水平高于单纯T2DM组,差异均有统计学意义(P＜0.05).Pearson相关性分析结果显示,血清CTRP9与ABI呈正相关,血清TNFR1、FGF23与ABI呈负相关(均P＜0.05).多因素Logistic回归分析结果显示,血清CTRP9降低,血清TNFR1、FGF23升高是T2DM患者LEAD发生的重要危险因素(P＜0.05).血清CTRP9、TNFR1、FGF23联合检测预测T2DM患者LEAD发生的AUC为0.902,灵敏度和特异性分别为0.731、0.886.结论 T2DM患者血清CTRP9水平降低,血清TNFR1、FGF23水平升高,血清CTRP9、TNFR1、FGF23水平变化与患者LEAD的发生密切相关,也是判断T2DM患者LEAD发生的重要生物学指标.     

FGF7亚家族在卵巢中的分布及卵泡发育过程中的作用

成纤维细胞生长因子(fibroblastgrowthfactor,FGF)家族是生长因子中的一个大家族,包括23个家族成员,具有相似的编码基因序列和空间结构,基于序列同源性和演变特征,将18种哺乳动物的FGFs分为6个亚家族,其中,FGF7亚家族(包括FGF3、FGF7、FGF10和FGF22)通过旁分泌途径发挥生理学作用。在女性生殖领域,国内外大多专注于研究FGFs对卵巢的影响。目前,已有报道显示FGF7和FGF10分布于卵母细胞和/或颗粒细胞,具有促进颗粒细胞增殖、抑制黄体酮和类固醇生成及分泌等功能,介导卵泡的募集和发育作用。对于其它两个成员FGF3和FGF22,其编码mRNA虽然在大鼠卵母细胞中表达,但是其对卵泡生长的生理作用尚不明确。     

连接蛋白2和FGF23在房颤介导心肌病兔心房组织中的表达

目的 探究连接蛋白2(JP2)和成纤维细胞生长因子23(FGF23)在房颤介导心肌病(AMC)兔中的表达规律。方法 通过左心房快速起搏法建立心房颤动(AF)模型,4周后行超声心动图检查,射血分数下降>10%纳入AMC组,否则为AF组,对照组只植入起搏器不起搏。最终成功建立AF动物模型11只,其中AF组6只,AMC组5只,对照组6只。超声心动图检测左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)等指标,酶联免疫吸附法(ELISA)检测血清JP2和FGF23水平。处死动物后,取心房组织,Western blot和RT-qPCR检测JP2和FGF23蛋白及mRNA表达。结果 与对照组相比,AMC组左房内径、右房内径、右室内径增大,LVEF降低,与AF组相比,AMC组LVEF降低,主动脉增宽,右室扩大。与对照组相比,AF组左房心肌细胞FGF23(P<0.001)、JP2(P<0.01)的表达均明显增加,而AMC组JP2表达降低(P<0.001)。与AF组相比,AMC组FGF23和JP2的表达下降。与对照组相比,AF组FGF23和J...     

青藤碱通过miR-23b-3p/FGF9诱导人类风湿关节炎成纤维细胞样滑膜细胞凋亡

目的:研究青藤碱(SIN)对人类风湿关节炎(RA)成纤维细胞样滑膜细胞(FLS)凋亡的影响及分子机制。方法:分离培养人RA FLS,用100 mg/L的脂多糖(LPS)处理记为LPS组;3.2 mmol/L SIN和100 mg/L LPS共同处理细胞,记为LPS+SIN组;不作任何处理的细胞作为空白(blank)组。将miR-con、miR-23b-3p、si-con和si-成纤维细胞生长因子9(FGF9)转染至RA FLS中再用100 mg/L LPS处理,分别记为LPS+miR-con组、LPS+miR-23b-3p组、LPS+si-con组和LPS+si-FGF9组;将anti-miR-con、anti-miR-23b-3p、pcDNA和pcDNA-FGF9转染至RA FLS中,再用3.2 mmol/L SIN和100 mg/L LPS共同处理,分别记为LPS+SIN+anti-miR-con组、LPS+SIN+anti-miR-23b-3p组、LPS+SIN+pcDNA组和LPS+SIN+pcDNA-FGF9组。CCK-8法检测细胞活力;集落形成实验检测细胞的集落形成数;Western blot法检测FGF9、cleaved caspase-3、Bax和Bcl-2蛋白水平;流式细胞术检测细胞凋亡;RT-qPCR检测miR-23b-3p和FGF9 mRNA的表达水平;双萤光素酶报告基因实验验证miR-23b-3p和FGF9的靶向关系。结果:SIN促进LPS诱导的RA FLS凋亡,抑制细胞增殖,上调miR-23b-3p表达,下调FGF9表达。miR-23b-3p靶向调控FGF9,过表达miR-23b-3p或沉默FGF9抑制LPS诱导的RA FLS增殖并促进细胞凋亡。干扰miR-23b-3p或过表达FGF9逆转了SIN对LPS诱导的RA FLS增殖和凋亡的影响。结论:青藤碱可通过miR-23b-3p/FGF9轴诱导RA FLS凋亡,抑制细胞增殖。     

脊椎动物成纤维细胞生长因子及其受体

成纤维细胞生长因子(FGFs)具有广泛的生物学功能,已知FGF家族至少包括23个因子(FGFs1-23);成纤维细胞生长因子受体(FGFRs)家族有3类:酪氨酸激酶受体类、富胱氨酸FGF受体和低亲和力受体肝素硫酸糖蛋白。FGFs和FGFRs一起组成了一个大而复杂的信号分子家族,具有促细胞分裂、促细胞运动和促形态形成的作用,在胚胎、组织发育和成熟中发挥着重要作用。     

CHF患者心功能相关指标与血清CA125、BNP、Hcy、FGF23水平的关系研究

目的探讨慢性心功能衰竭(CHF)患者血清糖类抗原125(CA125)、B型钠尿肽(BNP)、同型半胱氨酸(Hcy)、成纤维细胞生长因子23(FGF23)水平变化与患者心功能指标的关系。方法选取我院确诊的CHF患者126例(CHF组),选取正常健康人群60例作为对照组,检测研究对象的血清CA125、BNP、Hcy、FGF23水平,采用超声心动图测量两组的左室射血分数(LVEF%)、左室舒张末期内径(LVEDd)、左心室质量指数(LVMI),并探讨血清指标与心功能指标的相关性。结果 CHF组的血清CA125、BNP、Hcy、FGF23水平显著的高于对照组(P <0. 05);Ⅰ级、Ⅱ级CHF组的血清CA125、BNP、Hcy、FGF23水平显著的低于Ⅲ级和ⅣCHF组患者(P<0.05);CHF组患者血清CA125、BNP、Hcy与LVEF%呈负相关关系(P<0.05),血清CA125、BNP、Hcy与LVEDd呈正相关关系(P<0.05),血清BNP、Hcy、FGF23与LVMI呈正相关关系(P<0.05)。结论 CHF组的血清CA125、BNP、Hcy、FGF23水平较正常人群显著的升高并且与超声心动图指标具有一定相关性。     

成纤维细胞生长因子23和骨形态发生蛋白7介导维生素D受体表达下降在2型糖尿病并发骨质疏松大鼠发病中的作用

目的 探讨2型糖尿病并发骨质疏松大鼠肾和骨组织维生素D受体(VDR)、成纤维细胞生长因子(FGF)23、骨形态发生蛋白(BMP)7的表达及意义.方法 雌性Wistar大鼠随机分为假手术对照组(NS组)、单纯去卵巢组(NOVX组)、2型糖尿病假手术组(DS组)、2型糖尿病去卵巢组(D0VX 组).糖尿病组大鼠予高脂高糖饲料联合小剂量链脲佐菌素腹腔注射制备2型糖尿病模型,模型成功后去卵巢组行双侧卵巢切除术,去卵巢后4周、8周、12周末随机分批处死.用RT-PCR法观察各组肾和骨组织VDR、FGF23、BMP7的mRNA表达,Western免疫印迹法观察各组肾组织VDR、FGF23、BMP7蛋白表达.结果 成功制备2型糖尿病并发骨质疏松模型.随着时间延长,DS组和DOVX组肾和骨组织VDR、BMP7的mRNA表达和肾组织VDR、BMP7蛋白表达均较NS组和NOVX组降低,且以DOVX组表达最低(P＜0.05)；DS组和DOVX组骨组织FGF23的mRNA表达明显低于NS和NOVX组(0.566±0.059,0.452±0.057比1.008±0.068,0.520±0.049,P＜0.05),而DS组和DOVX组肾组织FGF23的mRNA和蛋白(1.034±0.071,1.136±0.112比0.919±0.086,0.952±0.143)表达明显高于NS和NOVX组,以DOVX组表达最高(P＜0.05).结论 FGF23和BMP7在肾和骨组织共同介导2型糖尿病并发骨质疏松大鼠维生素D受体表达中起不同作用.     

神经营养因子在早期人胚神经管发育中的定位表达

目的尽管在体外细胞培养实验中已经证实纤维细胞生长因子（FGF）、胰岛素样生长因子（IGF）、血管内皮生长因子（EGF）等因子具有神经营养作用,但是它们在神经管发育过程中的定位表达和变化规律仍然还不清楚,因此本实验将探索神经营养因子在人胚发育过程中的表达及意义。方法用23 d、45 d和56 d的人胚进行免疫组织化学ABC法染色,分析FGF、IGF、EGF在神经发育过程中的表达及意义。结果在早期人胚神经管发育中,室管膜层、中间层、边缘层均可见IGF、FGF、EGF表达,各层细胞胞质及细胞之间可见棕黄色免疫反应阳性物。结论在人胚早期发育的过程中,IGF起主导作用,EGF和FGF起协同作用,共同促进神经管的分化发育。     

Fibroblast growth factor 23 reduces expression of type IIa Na+/Pi co-transporter by signaling through a receptor functionally distinct from the known FGFRs in opossum kidney cells

Fibroblast growth factor (FGF) 23 is an important phosphaturic factor that inhibits inorganic phosphate (Pi) reabsorption from the renal proximal tubule. Its overproduction and proteolysis-resistant mutation such as R179Q cause tumor-induced osteomalacia and autosomal dominant hypophosphatemic rickets, respectively. To clarify the signaling mechanisms of FGF23 that mediate the reduction of Pi reabsorption, we inhibited the function of the known FGFRs in opossum kidney (OK-E) cells by expressing a dominant-negative (DN) form of FGFR. OK-E cells, which represent the renal proximal tubular cells, expressed all four known FGFRs. FGF23(R179Q) bound to and activated FGFR2, a prominent FGFR expressed in OK-E cells. The activated receptor transmitted a signal to increase the expression of type IIa Na(+)/Pi co-transporter and the Pi uptake. Expression of FGFR2(DN), which suppresses the major FGFR-mediated signal through the FRS2alpha-ERK pathway, reversed the function of FGF23(R179Q). When FGF23(R179Q) was applied to the basolateral side of polarized OK-E cells, regardless of the FGFR2(DN) expression, the apical Pi uptake decreased significantly. The apical application of FGF23(R179Q) in the polarized cells did not show such decrease but increase. The exogenously expressed FGFR2 was detectable only at the apical membrane. These results suggest that an FGF23 receptor, which is functionally distinct from the known FGFRs, is expressed at the basolateral membrane of OK-E cells.     

Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway

More than 300 million years ago, vertebrates emerged from the vast oceans to conquer gravity and the dry land. With this transition, new adaptations occurred that included ingenious changes in reproduction, waste secretion, and bone physiology. One new innovation, the egg shell, contained an ancestral protein (ovocleidin-116) that likely first appeared with the dinosaurs and was preserved through the theropod lineage in modern birds and reptiles. Ovocleidin-116 is an avian homolog of matrix extracellular phosphoglycoprotein (MEPE) and belongs to a group of proteins called short integrin-binding ligand-interacting glycoproteins (SIBLINGs). These proteins are all localized to a defined region on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of SIBLING proteins is an acidic serine aspartate-rich MEPE-associated motif (ASARM). Recent research has shown that the ASARM motif and the released ASARM peptide have regulatory roles in mineralization (bone and teeth), phosphate regulation, vascularization, soft-tissue calcification, osteoclastogenesis, mechanotransduction, and fat energy metabolism. The MEPE ASARM motif and peptide are physiological substrates for PHEX, a zinc metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets (HYP). There is evidence that PHEX interacts with another ASARM motif containing SIBLING protein, dentin matrix protein-1 (DMP1). DMP1 mutations cause bone and renal defects that are identical with the defects caused by a loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both HYP and ARHR, increased FGF23 expression plays a major role in the disease and in autosomal dominant hypophosphatemic rickets (ADHR), FGF23 half-life is increased by activating mutations. ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. FGF23 is a member of the fibroblast growth factor (FGF) family of cytokines, which surfaced 500 million years ago with the boney fish (i.e., teleosts) that do not contain SIBLING proteins. In terrestrial vertebrates, FGF23, like SIBLING proteins, is expressed in the osteocyte. The boney fish, however, are an-osteocytic, so a physiological bone-renal link with FGF23 and the SIBLINGs was cemented when life ventured from the oceans to the land during the Triassic period, approximately 300 million years ago. This link has been revealed by recent research that indicates a competitive displacement of a PHEX-DMP1 interaction by an ASARM peptide that leads to increased FGF23 expression. This review discusses the new discoveries that reveal a novel PHEX, DMP1, MEPE, ASARM peptide, and FGF23 bone-renal pathway. This pathway impacts not only bone formation, bone-renal mineralization, and renal phosphate homeostasis but also energy metabolism. The study of this new pathway is relevant for developing therapies for several diseases: bone-teeth mineral loss disorders, renal osteodystrophy, chronic kidney disease and bone mineralization disorders (CKD-MBD), end-stage renal diseases, ectopic arterial-calcification, cardiovascular disease renal calcification, diabetes, and obesity.     

Comparative genomics on mammalian Fgf6-Fgf23 locus

CCND2-C12orf5-FGF23-FGF6 locus at human chromosome 12p13.32 and CCND1-ORAOV1-FGF19-FGF4 locus at human chromosome 11q13.3 are paralogous regions (paralogons) within the human genome. FGF23 is the causative factor for tumor-induced osteomalacia (TIO), a paraneoplastic disorder characterized by hypophosphatemia and skeletal undermineralization, and also for autosomal dominant hypophosphatemic rickets (ADHR). Here, rat Fgf6 and Fgf23 complete coding sequences were determined by using bioinformatics. Rat Fgf6 and Fgf23 genes, consisting of three exons, were located within AC103292.6 rat genome sequence. Rat Fgf6 and Fgf23 genes were clustered in tail-to-head manner with an interval of about 52 kb. Human FGF6 and FGF23 genes were clustered in tail-to-head manner with an interval of about 54 kb. Intergenic conserved region (IGCR) within the FGF6-FGF23 gene cluster was identified based on the evolutionary conservation. Human FGF6-FGF23 IGCR (nucleotide position 111648-112242 of AC008012.8 genome sequence) and rat Fgf6-Fgf23 IGCR (nucleotide position 156318-156894 of AC103292.6 genome sequence) showed 77.6% total nucleotide identity. CP2, E47, CREB and PAX4 binding sites were conserved among human FGF6, rat Fgf6, and mouse Fgf6 promoters. GATA and E47 binding sites were conserved among human FGF23, rat Fgf23, and mouse Fgf23 promoters. Because mouse Fgf23 mRNA was expressed in dendritic cells and activated spleen, tumor infiltrating dendritic cells are candidate sources of FGF23 secretion in TIO patients. This is the first report on comparative genomics analyses on human FGF6-FGF23 gene cluster and rodents Fgf6-Fgf23 gene cluster.     

Expression and localization of fibroblast growth factor (FGF)23 and Klotho in the spleen: its physiological and functional implications

The FGF23–Klotho signaling axis is known to exert anti-aging effects via calcium–phosphorus metabolism. In mice deficient in FGF23–Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23–Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220⁺ CD21/CD35⁺ CD1d⁺ CD43^? marginal zone B cells. These cells also expressed FGF receptor 1, indicating that Klotho-positive B cells could respond to FGF23. Plasmacytoid dendritic cells (pDCs) with CD11c⁺ CD45R/B220⁺ CD11b^? CD8α^? were found to produce FGF23. Klotho-positive cells and FGF23-producing cells were present in close proximity to each other, suggesting that FGF23 produced by pDCs may act within a limited area. These findings indicate that FGF23–Klotho signaling could play a biological or immunological role in the spleen.     

Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses

Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process.     

Fibroblast growth factor (FGF)‐23 and fetuin‐A in calcified carotid atheroma

Voigt M, Fischer D‐C, Rimpau M, Schareck W & Haffner D
(2010) Histopathology 56 , 775–788
Fibroblast growth factor (FGF)‐23 and fetuin‐A in calcified carotid atheroma Aims: Human atheroma calcification occurs secondary to repetitive injury/remodelling of the vessel wall and might be initiated by adherence of mineral‐loaded fetuin‐A whether or not professional matrix mineralizing cells are present. The aim was to investigate the contribution of fibroblast growth factor (FGF)‐23 to ectopic mineralization. Methods and results: Serial sections of formalin‐fixed paraffin‐embedded human carotid atheroma (n = 54) were investigated with respect to (i) size and distribution of calcific deposits, (ii) indicators of chondrogenic/osteogenic transformation, and (iii) expression of fetuin‐A and FGF‐23. All specimens were calcified and SOX‐9, collagen type II, cathepsin‐K, fetuin‐A and FGF‐23 expression was seen in 46, 53, 53, 54 and 48 specimens, respectively. The intracellular detection of FGF‐23 (45/48) indicates local synthesis. Whereas fetuin‐A expression was seen also within areas of vascular smooth muscle actin‐positive cells adjacent to calcific deposits, FGF‐23 expression was apparently restricted to the mineralization‐prone areas. Both local expression and FGF‐23 serum concentrations were significantly associated with the degree of atheroma calcification. Conclusions: Besides the induction of bone islets and subsequent mineral deposition, severe remodelling of the vessel wall is sufficient to create a mineralizable fetuin‐A‐attracting microenvironment. FGF‐23 might contribute to the formation of proper mineral, i.e. control local phosphate concentration.     

FGF23: Mediator of poor prognosis in a sizeable subgroup of patients with castration-resistant prostate cancer presenting with severe hypophosphatemia?

Castration-resistant prostate cancer (CRPC) is an advanced and incurable stage of the second most frequently diagnosed malignancy in men globally. Current treatment options improve survival modestly but eventually fail due to intrinsic or acquired therapeutic resistance. A hypothesis is presented wherein circulating levels of fibroblast growth factor 23 (FGF23), an endocrine member of the fibroblast growth factor family with phosphaturic properties, are proposed as a prognostic and predictive marker to identify CRPC patients with poor prognosis that are amenable to FGF23 antibody therapy (FGF23i) or treatment with fibroblast growth factor receptor inhibitors (FGFRi). With respect to the latter, FGF23 may also serve as a pharmacodynamic marker enabling individualized FGFRi dosing.     

Fibroblast growth factor (FGF) 23 works as a phosphate-regulating hormone and is involved in the pathogenesis of several disorders of phosphate metabolism

Fibroblast growth factor (FGF) 23 was identified as the latest member of the FGF family. Subsequent studies showed that FGF23 reduces the serum phosphate level by suppressing proximal tubular phosphate reabsorption. This phosphaturic action of FGF23 derives from the suppressive effect of FGF23 on the expression of type 2a and 2c sodium-phosphate cotransporter in the brush border membrane of proximal tubules. At the same time, FGF23 reduces the serum level of 1,25-dihydroxyvitamin D [1,25(OH)2D] which results in suppressed intestinal phosphate absorption. Establishment of an enzyme-linked immunosorbent assay for FGF23 indicated that excess actions of FGF23 result in hypophosphatemic rickets/osteomalacia such as X-linked, autosomal dominant, autosomal recessive hypophosphatemic rickets/osteomalacia, and tumor-induced rickets/osteomalacia. In contrast, deficiency of FGF23 action causes hyperphosphatemic tumoral calcinosis. These results indicate that FGF23 is a hormone regulating serum phosphate and 1,25(OH)2D levels.     

The phosphate regulating hormone fibroblast growth factor-23

Over the last decade, the regulation of phosphate (Pi) homeostasis has been under intense investigation. By utilizing modern biochemical and genetic tools, the pathophysiological mechanisms behind several known hereditary and acquired hypo- and hyperphosphatemic diseases have been clarified. The results of these efforts have opened new insights into the causes of Pi dysregulation and hereby also the physiological mechanisms determining Pi homeostasis. Although several potential Pi-regulating proteins have been discovered and investigated, current data strongly argues for fibroblast growth factor-23 (FGF23), a hormonal factor produced in bone, as a particularly important regulator of Pi homeostasis. In this article, we review the discovery of the FGF23 protein, as well as its biochemistry, localization of production, receptor specificity and mechanisms of action.