FGF23在不同分期慢性肾脏病患者中的表达水平及其与左心室肥厚、PLSγ/calcineurin NFAT信号通路的关系

    Expression of FGF23 in patients at different stages of chronic kidney diseases and its correction with left ventricular hypertrophy, PLSγ/calcineurin NFAT signaling pathway

    • 摘要: 目的 探究针对慢性肾脏病不同分期患者FGF23水平的表达与左心室肥厚的相关性及对磷脂酶Sγ(PLSγ)/钙调神经磷酸活化T细胞核因子(NFAT)信号通路的影响。方法 筛选2016年10月至2018年9月来新疆医科大学第五附属医院就诊的CKD患者,将符合标准的的107例患者按照肾小球过滤率(GFR)将患者划分为2~5期,另选择同期就诊的健康正常人30例作为对照。分别检测GFR、血清成纤维细胞生长因子23(FGF23)、心脏结构和PLSγ/calcineurin NFAT通路信号,分析FGF23与心脏结构相关性及其对PLSγ/calcineurin NFAT信号通路的影响。结果 按照健康对照组、CKD 2期组、CKD 3期组、CKD 4期组、CKD 5期组顺序,患者GFR水平依次降低,FGF23水平依次升高,且各组间两指标均存在显著差异(P<0.01);随着患者CKD分期数增加,患者心脏右室各参数IVST、LVPWT、LVID、LVM和LVMI水平依次升高,且与健康对照组均存在显著差异(P<0.05),CKD 5期患者IVST、LVPWT和LVM均与其他组存在显著差异(P<0.05);Spearman相关性分析结果显示,107例CKD患者血清FGF23与LVID、IVS-R、LVPWT、LVM和LVMI呈正相关,相关系数分别为0.256、0.285、0.274、0.433和0.498,与E/A比值呈负相关,r=-0.431;CKD患者血清均表达神经钙蛋白和磷酸化NFAT(pNFAT)。结论 CKD2-5期患者中血清FGF23水平升高普遍存在,与左室肥厚显著相关,同时FGF23水平升高激活PLSγ/calcineurin NFAT信号通路。

       

      Abstract: Objective To investigate the correlation of the expression of FGF23 with left ventricular hypertrophy in patients at different stages of chronic kidney diseases, and its effect on the signaling pathway for phospholipase Sγ (PLSγ)/calmodulin-activated T cell nuclear factor (NFAT). Methods The CKD patients, who visited the Fifth Affiliated Hospital of Xinjiang Medical University from October 2016 to September 2018, were screened. A total of 107 patients who met the criteria were divided into various groups at 2-5 diseases stages according to their glomerular filtration rates (GFR), and 30 healthy people served as the control. GFR, serum fibroblast growth factor 23 (FGF23), cardiac structure and PLSγ/calcineurin NFAT signaling pathway were detected respectively, and the correlation of FGF23 with cardiac structure and its effect on PLSγ/calcineurin NFAT signaling pathway were analyzed. Results In an order of the healthy control group-stage CKD2 group -stage CKD3 group-stage CKD4 group-stage CKD5 group, the GFR levels of the patients decreased and the FGF23 level increased in turn, and there were significant differences in the two indicators between the two groups (P<0.01). With the increase of CKD stages of the patients, the levels of IVST, LVPWT, LVID, LVM and LVMI of the right ventricle increased in turn, and there were significant differences between the disease groups and the healthy control group (P<0.05). There were significant differences in IVST, LVPWT and LVM between the stage CKD 5 group and all the other groups (P<0.05). Spearman correlation analysis showed that serum FGF23 was positively correlated with LVID, IVS-R, LVPWT, LVM and LVMI in 107 patients with CKD, with a correlation coefficient of 0.256, 0.285, 0.274, 0.433 and 0.498; negatively correlated with E/A ratio, with r=-0.431; and, both calcineurin and phosphorylated NFAT (pNFAT) expressed in the serum in the CKD patients. Conclusions Serum FGF23 levels are prevalent in patients with stage 2-5 CKD, and significantly correlated with left ventricular hypertrophy. And elevated FGF23 levels may activate the PLSγ/calcineurin NFAT signaling pathway.

       

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