FGF23调控蛋鸡磷代谢的机制

Fibrobalst growth factor-23 (FGF23) is secreted by osteocytes and osteoblasts and is the member of FGF family. Phosphorus is the essential mineral element for the skeletal development, egg quality, and the development of osteoporosis in laying-type chickens. Our previous study indicates that FGF23 mainly expresses in bone, which is influenced by dietary phosphorus levels. The present study focuses on the regulating role of FGF23 in phosphorus metabolism of laying-type chickens. Firstly, the influences of nutritional and hormones factors on the expression and secretion of FGF23 will be investigated. Then the expression of FGF23 in E. Coli and the purification of FGF23 are conducted. Thereafter, the effects of FGF23 on renal phosphorus re-absorption and secretion and on intestinal phosphorus absorption are determined respectively. The absorption of phosphorus will be investigated with different animal models and cell culture models. The functions of relevant signaling pathways are evaluated by the activation or inhibition of crucial signal molecules. The result of the present study will demonstrate the regulating effect of FGF23 in phosphorus metabolism of laying-type chickens by elucidating the crosstalk between FGF23 and 1,25(OH)2D3/PTH network and provides fundamental basis for the development of new techniques to improve dietary phosphorus utilization and reduce manure phosphorus excretion.

FGF23是由骨骼分泌的成纤维细胞生长因子（FGF）。磷是蛋鸡必需的矿物元素，与蛋鸡骨骼发育、蛋壳质量和骨质疏松症的发生与发展密切相关。申请人前期研究发现，FGF23在蛋鸡骨骼中表达丰度最高，并受日粮磷水平影响，由此提出的科学问题是：FGF23在蛋鸡磷代谢调控中的作用与机制是什么？拟从以下三个方面开展研究：（1）FGF23表达分泌规律及调控机制；（2）构建FGF23重组蛋白表达系统，研究FGF23影响肾脏磷重吸收与排泄的机制；（3）FGF23调控肠道磷吸收的机制。拟通过动物与细胞培养试验相结合，确定FGF23影响磷吸收规律；通过激活与抑制相关信号通路中的信号分子，确定FGF23调控途径和对1,25(OH)2D3和PTH调控通路的影响。本研究可以确立FGF23对蛋鸡磷代谢调控作用，探明FGF23与1,25(OH)2D3/PTH调控网络的对话，为提高日粮磷利用率和减少粪尿中磷排放提供理论依据。

磷是蛋鸡必需的矿物元素，与蛋鸡骨骼发育、蛋壳质量和骨质疏松症的发生与发展密切相关；磷矿是不可再生资源，饲料中无机磷的添加使用造成粪便中磷排放增加。FGF23是由骨骼分泌的成纤维细胞生长因子（FGF），参与了机体磷代谢调控。本研究围绕科学问题：“FGF23在蛋鸡磷代谢调控中的作用与机制是什么”，开展了系列研究，研究了蛋鸡钙磷代谢规律，分析了蛋鸡不同发育与产蛋阶段骨骼FGF23表达规律，研究了日粮钙磷水平对骨骼FGF23表达的影响规律，考察了影响成骨细胞FGF23表达的因素，研究FGF23 在维生素D诱导成骨细胞分化中的作用、FGF23调控成骨细胞矿化的信号途径和FGF23在免疫应激影响骨骼钙磷代谢中的作用。通过本项目研究，探明了FGF23在蛋鸡生长发育和全产蛋周期内的表达规律，初步建立了由日粮磷、1,25(OH)2D3、PTH和TNF-α 构成的FGF23表达调控网络；确定了 FGF23影响磷吸收的规律和FGF23调控成骨细胞矿化的信号途径，证明FGF23在蛋鸡钙磷代谢中具有重要的调控作用。研究实现了预定的研究目标，丰富了家禽钙磷代谢调控理论，证明FGF23是一个重要磷代谢调控靶点，对于提高饲料磷转化效率、降低粪便磷排放水平具有重要的指导意义。通过本项目研究，发表 SCI 收录论文15篇，培养博士研究生1人，硕士研究生5人，实现了预期目标。