Glycerol-3-phosphate and fibroblast growth factor 23 regulation. Issue 4 (July 2021) - Simic, Petra
Abstract : Purpose of review: Both classical and nonclassical factors regulate fibroblast growth factor 23 (FGF23), with impacts on gene expression and proteolytic cleavage. Here, we review recent publications that extend current knowledge on these factors. Recent findings: Emerging nonclassical FGF23 regulators such as erythropoietin cause a balanced increase in FGF23 expression and cleavage, with minimal or no increase in biologically active intact FGF23 (iFGF23) in blood. However, circulating FGF23 profiles may not reflect the bone marrow microenvironment. For example, granulocyte colony-stimulating factor increases local marrow iFGF23 levels without impacting circulating iFGF23 levels. The view that phosphate does not increase bone FGF23 production also warrants reconsideration, as phosphate can reduce iFGF23 cleavage and phosphate-containing calciprotein particles increase FGF23 expression. Finally, a screen of renal venous plasma identifies glycerol-3-phosphate as a kidney-derived molecule that circulates to bone and bone marrow, where it is converted to lysophosphatidic acid and signals through a G-protein coupled receptor to increase FGF23 synthesis. Summary: FGF23 regulation is complex, requiring consideration of known and emerging stimuli, expression and cleavage, and circulating and local levels. Recent work identifies glycerol-3-phosphate as an FGF23 regulator derived from the injured kidney; whether it participates in FGF23 production downstream of classical or nonclassical factors requires further study.