University of Hohenheim, Department of Physiology, Stuttgart, Germany.
Fourth Department of Internal Medicine and Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Exp Clin Endocrinol Diabetes. 2024 Feb;132(2):91-97. doi: 10.1055/a-2237-8863. Epub 2024 Feb 19.
Fibroblast growth factor 23 (FGF23) is a major regulator of phosphate and vitamin D metabolism in the kidney, and its higher levels in plasma are associated with poorer outcomes in kidney and cardiovascular diseases. It is produced by bone cells upon enhanced oxidative stress and inhibits renal phosphate reabsorption and calcitriol (active form of vitamin D) production. Bilirubin, the final product of the heme catabolic pathway in the vascular bed, has versatile biological functions, including antioxidant and anti-inflammatory effects. This study explored whether bilirubin alters FGF23 production.
Experiments were performed using UMR106 osteoblast-like cells. transcript levels were determined by quantitative real-time polymerase chain reaction, C-terminal and intact FGF23 protein levels were determined by enzyme-linked immunosorbent assay, and cellular oxidative stress was assessed by CellROX assay.
Unconjugated bilirubin down-regulated gene transcription and FGF23 protein abundance; these effects were paralleled by lower cellular oxidative stress levels. Also, conjugated bilirubin reduced mRNA abundance.
Bilirubin down-regulates FGF23 production in UMR106 cells, an effect likely to be dependent on the reduction of cellular oxidative stress.
成纤维细胞生长因子 23（FGF23）是肾脏中磷和维生素 D 代谢的主要调节剂，其在血浆中的水平较高与肾脏和心血管疾病的预后较差有关。它由骨细胞在氧化应激增强时产生，并抑制肾脏对磷酸盐的重吸收和 1,25-二羟维生素 D [活性形式的维生素 D]的产生。胆红素是血管床中血红素分解代谢途径的终产物，具有多种生物学功能，包括抗氧化和抗炎作用。本研究探讨了胆红素是否改变 FGF23 的产生。
使用 UMR106 成骨样细胞进行实验。通过实时定量聚合酶链反应测定 转录水平，通过酶联免疫吸附试验测定 C 端和完整的 FGF23 蛋白水平，通过 CellROX 测定细胞氧化应激。
未结合胆红素下调 基因转录和 FGF23 蛋白丰度；这些作用与较低的细胞氧化应激水平平行。此外，结合胆红素降低了 mRNA 的丰度。
胆红素下调 UMR106 细胞中的 FGF23 产生，这种作用可能依赖于细胞氧化应激的降低。
