Wu Vin-Cent, Peng Kang-Yung, Chen Tsu-I, Sun Chiao-Yin, Liao Hung-Wei, Chan Chieh-Kai, Lin Yen-Hung, Liou Hung-Hsiang, Chueh Jeff S
Department of Internal Medicine and.
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
JCI Insight. 2025 Feb 24;10(4):e166461. doi: 10.1172/jci.insight.166461.
This study examined the involvement of fibroblast growth factor-23 (FGF-23) in primary aldosteronism (PA), a condition characterized by elevated aldosterone levels and hypertension. We recruited patients with unilateral PA (uPA) and observed increased levels of C-terminal FGF-23 (cFGF-23) and C-terminal to intact FGF-23 (iFGF-23) in patients with uPA compared with essential hypertension control participants. Elevated preoperative cFGF-23 levels were associated with adverse outcomes, including mortality and cardiovascular or kidney events. Plasma cFGF-23 levels demonstrated a nonlinear rise with aldosterone, but iFGF-23 levels were not correlated with plasma aldosterone concentration. Higher cFGF-23 levels independently predicted hypertension remission after adrenalectomy for patients with uPA. Patients with uPA, who exhibited elevated cFGF-23 levels, had decreased levels after adrenalectomy. In cell cultures, aldosterone enhanced cleavage of iFGF-23, leading to increased levels of cFGF-23 fragments, an effect mitigated by silencing of family with sequence similarity 20, member C (FAM20C). However, the enhancement of cFGF-23 levels remained unaffected by the furin inhibitor. The study suggests that aldosterone influences FGF-23 phosphorylation by interacting with FAM20C, with docking experiments indicating aldosterone's binding to FAM20C. This work highlights that patients with uPA with elevated cFGF-23 levels are associated with cardiovascular risks, and adrenalectomy reduces cFGF-23. Aldosterone likely promotes cFGF-23 production through FAM20C-mediated phosphorylation of iFGF-23.
本研究探讨了成纤维细胞生长因子23（FGF - 23）在原发性醛固酮增多症（PA）中的作用，原发性醛固酮增多症的特征是醛固酮水平升高和高血压。我们招募了单侧PA（uPA）患者，发现与原发性高血压对照参与者相比，uPA患者的C末端FGF - 23（cFGF - 23）和完整FGF - 23（iFGF - 23）的C末端水平升高。术前cFGF - 23水平升高与不良结局相关，包括死亡率以及心血管或肾脏事件。血浆cFGF - 23水平随醛固酮呈非线性升高，但iFGF - 23水平与血浆醛固酮浓度无关。较高的cFGF - 23水平可独立预测uPA患者肾上腺切除术后高血压缓解情况。cFGF - 23水平升高的uPA患者在肾上腺切除术后水平下降。在细胞培养中，醛固酮增强了iFGF - 23的裂解，导致cFGF - 23片段水平升高，这一效应可通过沉默序列相似性家族20成员C（FAM20C）来减轻。然而，cFGF - 23水平的升高不受弗林蛋白酶抑制剂的影响。该研究表明，醛固酮通过与FAM20C相互作用影响FGF - 23磷酸化，对接实验表明醛固酮与FAM20C结合。这项工作强调，cFGF - 23水平升高的uPA患者与心血管风险相关，肾上腺切除术可降低cFGF - 23水平。醛固酮可能通过FAM20C介导的iFGF - 23磷酸化促进cFGF - 23生成。
