Molecular Physiology of the Hypocalcemic Action of Fibroblast Growth Factor 23 in Zebrafish (Danio rerio).
Fibroblast growth factor 23 (FGF23), a hormone required for phosphorus metabolism, was recently proposed to act on Ca2+ uptake; however, the available evidence of how FGF23 controls the body fluid Ca2+ homeostasis needs to be further clarified. The use of zebrafish as a model system revealed that FGF23 is specifically expressed in the corpuscles of Stannius (CS), an organ involved in Ca2+ homeostasis in fish, and that its expression is stimulated by ambient water with a high Ca2+ level. The overexpression of FGF23 inhibited Ca2+ uptake by downregulating the messenger RNA (mRNA) expression of epithelium calcium channel. Calcium-sensing receptor (CaSR), which senses changes in extracellular Ca2+ levels and modulates calciotropic hormones in organs controlling Ca2+ homeostasis in vertebrates, was found to be coexpressed with FGF23 in the CS. In addition, upregulated expression of FGF23 mRNA was detected in morphants of stanniocalcin 1 (stc1, another hypocalcemic factor synthesized in the CS), and knockdown of CaSR suppressed such upregulation and enhanced Ca2+ uptake. Taken together, our data indicate that FGF23 functions as a hypocalcemic hormone in zebrafish and that the CaSR/STC1-FGF23 axis is involved in body fluid Ca2+ homeostasis in vertebrates.
National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan.
Chia-Hao
CH
Lin
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan, ROC.
Huei-Jyun
HJ
Hu
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan, ROC.
Pung-Pung
PP
Hwang
D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics*; D004625:Embryo, Nonmammalian; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006996:Hypocalcemia / Q000235:genetics* / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
D006023:Glycoproteins; D044169:Receptors, Calcium-Sensing; D005346:Fibroblast Growth Factors; C051795:teleocalcin; D000089703:Fibroblast Growth Factor-23; D002118:Calcium