The relevance of chorein for FGF23 production and Ca2+/phosphate metabolism

成纤维细胞生长因子23（FGF 23）是由骨细胞产生的，抑制肾脏磷酸盐重吸收和骨化三醇（生物活性维生素D）的形成，沿着其专性辅助受体Klotho。FGF 23或Klotho缺乏导致快速衰老，寿命短，以及大量衰老相关疾病的发作。在许多急性和慢性人类疾病中观察到FGF 23水平的增加。FGF 23在细胞水平上的合成调控尚不明确。舞蹈素是一种在不同组织中表达的蛋白质，舞蹈素缺乏或功能障碍可导致舞蹈病-棘红细胞增多症，这是一种遗传性疾病，其特征是运动异常和棘红细胞、变形的红细胞。细胞功能尚不完全清楚。根据我们已发表的研究，chorein调节肌动蛋白细胞骨架的聚合。本课题旨在阐明：（i）chorein依赖的FGF 23形成的细胞和分子机制;（ii）chorein与Ca ~（2+）/磷酸盐代谢、骨化三醇合成和血管钙化的生理相关性;（iii）chorein对肾脏和肾脏膜转运的影响。该项目有望揭示舞蹈素的新细胞功能。此外，它将确定新的FGF 23调节剂。这将有助于更好地理解FGF 23的生理和病理生理作用。

Fibroblast growth factor 23 (FGF23) is produced by bone cells andinhibits renal phosphate reabsorption and formation of calcitriol,biologically active vitamin D, along with its obligatory co-receptorKlotho. FGF23 or Klotho deficiency result in rapid aging, a short lifespan, and the onset of a plethora of aging-associated diseases. Anincrease in FGF23 levels is observed in many acute and chronichuman disorders. The regulation of FGF23 synthesis on a cellularlevel is ill-defined. Chorein is a protein expressed in different tissues.Chorein deficiency or malfunction lead to chorea-acanthocytosis, arare genetic disorder characterized by abnormal movements andacanthocytes, misshaped erythrocytes. Cellular functions of choreinare incompletely understood. According to our published studieschorein regulates the polymerization of actin cytoskeleton. Moreover,the reorganization of the actin cytoskeleton affects FGF23 production.The present project aims at elucidating (i) the cellular and molecularmechanisms of chorein-dependent FGF23 formation, (ii) thephysiological relevance of chorein for Ca2+/phosphate metabolism,calcitriol synthesis and vascular calcification, and (iii) the impact ofchorein on renal and intestinael membrane transport. The project isexpected to uncover novel cellular functions of chorein. Moreover, itwill identify novel regulators of FGF23. This will contribute to a betterunderstanding of the physiological and pathophysiological role ofFGF23.