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

  • Applied microbial and cell physiology
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Abstract

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.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81071800), the Natural Science Foundation of Zhejiang Province of China (LY14H310013), the Team Project of Natural Science Foundation of Guangdong Province of China (S2013030013315), Guangdong Provincial “Thousand-Hundred-Ten Talent Project” (X. Wu), Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University.

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Authors and Affiliations

  1. Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, 510632, China

    Tao Huang, Xiaomian Lin, Quchou Li, Wu Luo, Li Song, Xiangpeng Tan, Wenhui Wang & Xiaoping Wu

  2. School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, China

    Xiaokun Li & Xiaoping Wu

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  1. Tao Huang
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  2. Xiaomian Lin
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  3. Quchou Li
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  4. Wu Luo
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  5. Li Song
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  6. Xiangpeng Tan
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  7. Wenhui Wang
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  8. Xiaokun Li
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  9. Xiaoping Wu
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Correspondence to Xiaoping Wu.

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Tao Huang, Xiaomian Lin, and Quchou Li contributed equally to this work.

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Huang, T., Lin, X., Li, Q. et al. Selection of a novel FGF23-binding peptide antagonizing the inhibitory effect of FGF23 on phosphate uptake. Appl Microbiol Biotechnol 99, 3169–3177 (2015). https://doi.org/10.1007/s00253-014-6283-5

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  • DOI: https://doi.org/10.1007/s00253-014-6283-5

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