Role of fibroblast growth factor 23 in secondary hyperparathyroidism / 中华肾脏病杂志

ABSTRACT

Objective To investigate the role of fibroblast growth factor-23 (FGF23) in secondary hyperparathyroidism (SHPT). Methods (1)Serum FGF23 and intact parathyroid hormone (iPTH)from 38 maintenance hemodialysis (MHD) patients were measured by ELISA and chemiluminescence enzyme immunoassay respectively.(2) Parathyroid cells from six SHPT patients underwent parathyroidectomy with forearm autotrlansplantation were cultured for 24 h,then were induced by 0.1 mg/L FGF23.The supernatant was collected at 0.6,12,24 and 48 h respectively. The concentration of iPTH was measured by chemiluminescence enzyme immunoassay. (3)Protein expression of Klotho,FGFR1,FGFR3,GATA-3 and PCNA in parathyroid tissue from 33 SHPT eases and 3 healthy people were detected by immunohistochemistry SP and PV methods respectively. Positive cell rate and absorbance were calculated. Results (1) Serum FGF23 [(3901.85±2618.11) ng/L] was positively correlated with serum iPTH [(460.00±489.77) ng/L] in MHD patients. (2) 0.1 mg/L FGF23 suppressed iPTH secretion of parathyroid cells only at 24 h time point in vitro (P<0.05). (3) Expression of GATA-3, FGFR3, Klotho and PCNA was significantly increased and FGFRl was signiticantly decreased in parathyroid tissue of SHPT-patients as compared to healthy people. (4) Positive cell rate of GATA-3 was positively correlated with iPTH (r~2=0.1901, P=0.0425) and PCNA (r~2=0.2584, P=0.0025). Klotho was positively correlated with FGFRI and FGFR3 (r~2=0.2046, P=0.0082;r~2=0.2833, P=0.0014). PCNA was negatively correlated with FGFR1 (r~2=0.1292, P=0.0399) and positively correlated with FGFR3 (r~2=0.1226, P=0.0457). FGFR1 was negatively correlated with serum phosphate (r~2=0.2329, P=0.0044) and positively correlated with serum calcium (r~2=0.1422, P=0.0305). Conclusions FGF23 level is positively correlated with iPTH level in MHD patients. FGF23 can inhibit iPTH secretion of parathyroid cells in a weak and short way, which may be associated with the proliferation of GATA-3 positive cells and parathyroid cells, the up-regulation of FGFR3 and the down-regulation of FGFR1 expression.