caa a22 4500 605500266 CHVBK 20210128100555.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00253-014-6283-5 doi (NATIONALLICENCE)springer-10.1007/s00253-014-6283-5 Selection of a novel FGF23-binding peptide antagonizing the inhibitory effect of FGF23 on phosphate uptake [Elektronische Daten] [Tao Huang, Xiaomian Lin, Quchou Li, Wu Luo, Li Song, Xiangpeng Tan, Wenhui Wang, Xiaokun Li, Xiaoping Wu] Fibroblast growth factor 23 (FGF23) is a bone-derived endocrine regulator of phosphate homeostasis and has been considered as a potential therapeutic target for hypophosphatemic disorders. Herein, we isolated a novel FGF23-binding peptide by screening a phage display library with FGF23180-205, the minimal epitope of FGF23 binding to the binary fibroblast growth factor receptor (FGFR)-Klotho complex. The corresponding peptide (referred to as 23-b6) showed high homology to the immunoglobulin-like (Ig-like) domain III (D3) of FGFR1c, the predominant receptor mediating the phosphaturic activity of FGF23. The 23-b6 peptide and panning target FGF23180-205 carried opposite charges and shared similar hydrophilic profiles. Functional analysis indicated that synthetic 23-b6 peptide exhibited antagonistic effect on the inhibition of phosphate uptake by FGF23 in opossum kidney cells (OK cells). The mechanisms of 23-b6 peptide impairing the bioactivity of FGF23 involved blockade of the activation of Erk cascade and up-regulation of NaPi-2a and NaPi-2c expression in OK cells. Our results demonstrate that the 23-b6 peptide is a potent FGF23 antagonist with increased effect on phosphate uptake in kidney cells and might have therapeutic potentials in hypophosphatemic disorders characterized by an abnormally high level of FGF23. Springer-Verlag Berlin Heidelberg, 2014 Fibroblast growth factor 23 nationallicence Phage display nationallicence Phosphate uptake nationallicence Hypophosphatemia nationallicence Huang Tao Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut Lin Xiaomian Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut Li Quchou Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut Luo Wu Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut Song Li Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut Tan Xiangpeng Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut Wang Wenhui Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut Li Xiaokun School of Pharmaceutical Science, Wenzhou Medical University, 325035, Wenzhou, China aut Wu Xiaoping Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/7(2015-04-01), 3169-3177 0175-7598 99:7<3169 2015 99 253 https://doi.org/10.1007/s00253-014-6283-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-014-6283-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Huang Tao Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut NATIONALLICENCE 700 1- Lin Xiaomian Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut NATIONALLICENCE 700 1- Li Quchou Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut NATIONALLICENCE 700 1- Luo Wu Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut NATIONALLICENCE 700 1- Song Li Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut NATIONALLICENCE 700 1- Tan Xiangpeng Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut NATIONALLICENCE 700 1- Wang Wenhui Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut NATIONALLICENCE 700 1- Li Xiaokun School of Pharmaceutical Science, Wenzhou Medical University, 325035, Wenzhou, China aut NATIONALLICENCE 700 1- Wu Xiaoping Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/7(2015-04-01), 3169-3177 0175-7598 99:7<3169 2015 99 253