Selection of a novel FGF23-binding peptide antagonizing the inhibitory effect of FGF23 on phosphate uptake

Verfasser / Beitragende:
[Tao Huang, Xiaomian Lin, Quchou Li, Wu Luo, Li Song, Xiangpeng Tan, Wenhui Wang, Xiaokun Li, Xiaoping Wu]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/7(2015-04-01), 3169-3177
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00253-014-6283-5  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-014-6283-5 
245 0 0 |a Selection of a novel FGF23-binding peptide antagonizing the inhibitory effect of FGF23 on phosphate uptake  |h [Elektronische Daten]  |c [Tao Huang, Xiaomian Lin, Quchou Li, Wu Luo, Li Song, Xiangpeng Tan, Wenhui Wang, Xiaokun Li, Xiaoping Wu] 
520 3 |a 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. 
540 |a Springer-Verlag Berlin Heidelberg, 2014 
690 7 |a Fibroblast growth factor 23  |2 nationallicence 
690 7 |a Phage display  |2 nationallicence 
690 7 |a Phosphate uptake  |2 nationallicence 
690 7 |a Hypophosphatemia  |2 nationallicence 
700 1 |a Huang  |D Tao  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
700 1 |a Lin  |D Xiaomian  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
700 1 |a Li  |D Quchou  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
700 1 |a Luo  |D Wu  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
700 1 |a Song  |D Li  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
700 1 |a Tan  |D Xiangpeng  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
700 1 |a Wang  |D Wenhui  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
700 1 |a Li  |D Xiaokun  |u School of Pharmaceutical Science, Wenzhou Medical University, 325035, Wenzhou, China  |4 aut 
700 1 |a Wu  |D Xiaoping  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/7(2015-04-01), 3169-3177  |x 0175-7598  |q 99:7<3169  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-014-6283-5  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-014-6283-5  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Huang  |D Tao  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lin  |D Xiaomian  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Li  |D Quchou  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Luo  |D Wu  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Song  |D Li  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tan  |D Xiangpeng  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Wenhui  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Li  |D Xiaokun  |u School of Pharmaceutical Science, Wenzhou Medical University, 325035, Wenzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wu  |D Xiaoping  |u Institute of Tissue Transplantation and Immunology, Jinan University, 510632, Guangzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/7(2015-04-01), 3169-3177  |x 0175-7598  |q 99:7<3169  |1 2015  |2 99  |o 253