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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.