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Chemerin-Derived Peptide C-20 Suppressed Gonadal Steroidogenesis

Authors

  • Lei Li,

    1. Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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    • These authors contributed equally to this work.
  • Chen Huang,

    1. Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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    • These authors contributed equally to this work.
  • Xu Zhang,

    1. Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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  • Jiangbo Wang,

    1. Affiliated Hospital of ChiFeng University, Inner Mongolia, China
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  • Ping Ma,

    1. Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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  • Yongjun Liu,

    1. Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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  • Tianxia Xiao,

    1. Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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  • Brian A. Zabel,

    1. Palo Alto Institute for Research and Education, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
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  • Jian V. Zhang

    Corresponding author
    1. Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
    2. Shenzhen Engineering Laboratory of Single-molecule Detection and Instrument Development, Shenzhen, China
    3. Guangdong Key Laboratory of Nanomedicine, Guangdong, China
    • Correspondence

      Jian V. Zhang, Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

      E-mail: jian.zhang@siat.ac.cn

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Abstract

Problem

Chemerin is a novel chemo-attractant and adipokine involved in leukocyte recruitment, inflammation, adipogenesis, lipid/carbohydrate metabolism, and reproduction. Based on the bioinformatic search for putative small peptides in the conserved region of pre-pro-chemerin, an evolutionary conserved region flanked by potential convertase cleavage sites was identified and we named it as C-20. The binding capacity of C-20 to chemerin receptors and its potential bioactivities were investigated in this study.

Method of study

Radioligand binding assay, receptor internalization assay, and early response gene C-FOS simulation, cAMP assay were carried out in chemokine-like receptor 1 (CMKLR1)/HEK293 transfectants and G protein-coupled receptor 1 (GPR1)/HEK293 transfectants. In vitro transwell chemotaxis assay in CMKLR1/L1.2 transfectants, primary Leydig cell culture, and antral follicle culture was explored to investigate the bioactivity of C-20.

Results

C-20 bound to chemerin receptors CMKLR1 and GPR1 with high affinity triggered CMKLR1 internalization and stimulated subsequent signal C-FOS expression and cAMP production. C-20, such as chemerin, showed CMKLR1-dependent chemotactic property. Furthermore, in primary Leydig cells and antral follicles, C-20 showed similar but less potent suppressive effect on human chorionic gonadotropin-stimulated testosterone production and progesterone production, compared with chemerin.

Conclusion

The novel chemerin-derived C-20 peptide binds to chemerin receptors CMKLR1 and GPR1 and showed similar but less potent bioactivity in chemotaxis and the suppression of gonadal steroidogenesis, suggesting that after optimization, C-20 is possible to be a useful experimental tool for the understanding of the biological functions of chemerin/CMKLR1 and chemerin/GPR1 signaling.

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