College of Animal Science and Technology, Northwest A&F University, 22 XiNong Road, Yangling, Shaanxi 712100, China.
Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI 53706.
Poult Sci. 2019 Nov 1;98(11):5691-5699. doi: 10.3382/ps/pez353.
Targeting fibroblast growth factor 23 (FGF-23) signaling pathway is of interest in controlling body phosphate metabolism. This study investigated the effect of anti-fibroblast growth factor receptor 1 (FGFR1, major FGF-23 receptor in the kidney) antibodies on phosphate metabolism. White Leghorn laying hens (65-wk-old) were vaccinated with either a FGFR1 peptide vaccine (five 8-amino-acid peptides were selected, CrZ-1:LPEDPRWE, CrZ-2:LDKDKPNR, CrZ-3:RRPPGMEY, CrZ-4:GSPYPGVP, and CrZ-5:RMDKPSNC) or adjuvant control. At peak antibody titer, hens were artificially inseminated. Chicks from control-vaccinated hens were fed either a non-phytate phosphorus (nPP) sufficient (nPP = 0.45%, positive control) or deficient (nPP = 0.20%, negative control) diet, while chicks from each of the FGFR1 peptide vaccinated hens were fed with the above nPP-deficient diet, for 14 D. When compared to control hens, plasma phosphate in CrZ-1, CrZ-2, CrZ-3, CrZ-4, and CrZ-5 vaccinated hens were decreased by 33, 30, 24, 20, and 26%, respectively (P < 0.05); egg weight in CrZ-2 and CrZ-5 vaccinated hens were increased by 6 and 7%, respectively (P < 0.05); egg production in CrZ-3, CrZ-4, and CrZ-5 vaccinated hens tended to decrease (P = 0.085; decreased by 14, 15, and 13%, respectively). When compared to positive control, chicks from all other groups had decreased body weight gain (BWG) and feed intake (FI) during 1 to 14 D, and had decreased plasma phosphate, tibiotarsus ash, and 24-h phosphorus excretion on day 14. When compared to negative control, BWG of CrZ-1, CrZ-2, CrZ-3, and CrZ-4 antibody chicks were decreased by 23, 28, 26, and 20%, respectively (P < 0.05); FI of CrZ-1, CrZ-2, and CrZ-3 antibody chicks were decreased by 15, 15, and 18%, respectively (P < 0.05); plasma phosphate of CrZ-5 antibody chicks were decreased by 26% (P < 0.05); plasma FGF-23 levels of CrZ-4 antibody chicks were increased by 18% (P < 0.05); tibiotarsus ash content of CrZ-2, CrZ-3, and CrZ-4 antibody chicks were decreased by 20, 20, and 21%, respectively (P < 0.05). In conclusion, anti-FGFR1 peptide antibodies decreased egg production of hens and growth performance of their progeny chicks probably by activating FGF-23 signaling and stimulating FGF-23 production.
靶向成纤维细胞生长因子 23（FGF-23）信号通路对于控制体内磷酸盐代谢具有重要意义。本研究探讨了抗成纤维细胞生长因子受体 1（FGFR1，肾脏中主要的 FGF-23 受体）抗体对磷酸盐代谢的影响。白来航产蛋母鸡（65 周龄）接种 FGFR1 肽疫苗（选择了 5 个 8 个氨基酸肽，CrZ-1：LPEDPRWE、CrZ-2：LDKDKPNR、CrZ-3：RRPPGMEY、CrZ-4：GSPYPGVP 和 CrZ-5：RMDKPSNC）或佐剂对照。在抗体滴度峰值时，母鸡进行人工授精。来自对照疫苗接种母鸡的小鸡分别喂食非植酸磷（nPP）充足（nPP = 0.45%，阳性对照）或不足（nPP = 0.20%，阴性对照）饮食，而来自每个 FGFR1 肽疫苗接种母鸡的小鸡则喂食上述 nPP 不足饮食，持续 14 天。与对照母鸡相比，CrZ-1、CrZ-2、CrZ-3、CrZ-4 和 CrZ-5 疫苗接种母鸡的血浆磷酸盐分别降低了 33%、30%、24%、20%和 26%（P<0.05）；CrZ-2 和 CrZ-5 疫苗接种母鸡的鸡蛋重量分别增加了 6%和 7%（P<0.05）；CrZ-3、CrZ-4 和 CrZ-5 疫苗接种母鸡的产蛋量呈下降趋势（P=0.085；分别下降了 14%、15%和 13%）。与阳性对照相比，所有其他组的小鸡在 1 至 14 天期间的体重增加（BWG）和饲料摄入（FI）均降低，血浆磷酸盐、胫骨灰分和 14 天 24 小时磷排泄也降低。与阴性对照相比，CrZ-1、CrZ-2、CrZ-3 和 CrZ-4 抗体组小鸡的 BWG 分别降低了 23%、28%、26%和 20%（P<0.05）；CrZ-1、CrZ-2 和 CrZ-3 抗体组小鸡的 FI 分别降低了 15%、15%和 18%（P<0.05）；CrZ-5 抗体组小鸡的血浆磷酸盐降低了 26%（P<0.05）；CrZ-4 抗体组小鸡的血浆 FGF-23 水平增加了 18%（P<0.05）；CrZ-2、CrZ-3 和 CrZ-4 抗体组小鸡的胫骨灰分含量分别降低了 20%、20%和 21%（P<0.05）。总之，抗 FGFR1 肽抗体可能通过激活 FGF-23 信号通路和刺激 FGF-23 产生，降低母鸡产蛋量和其后代小鸡的生长性能。
