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Fibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis

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  • Jaiwoo Lee

    (Seoul National University)

  • Junho Byun

    (Seoul National University)

  • Gayong Shim

    (Soongsil University)

  • Yu-Kyoung Oh

    (Seoul National University)

Abstract

In liver fibrosis, activated hepatic stellate cells are known to overexpress fibroblast activation protein. Here we report a targeted antifibrotic peptide-delivery system in which fibroblast activation protein, which is overexpressed in fibrotic regions of the liver, liberates the antifibrotic peptide melittin by cleaving a fibroblast activation protein-specific site in the peptide. The promelittin peptide is linked to pegylated and maleimide-functionalized liposomes, resulting in promelittin-modified liposomes. The promelittin-modified liposomes were effective in reducing the viability of activated hepatic stellate cells but not that of control cells. In three types of liver fibrosis mouse models, intravenously administered promelittin-modified liposomes significantly reduces fibrotic regions. In addition, in the bile duct ligation mouse model promelittin-modified liposome-treatment increases overall survival. Although this peptide-delivery concept was tested for liver fibrosis, it can potentially be adapted to other fibrotic diseases.

Suggested Citation

  • Jaiwoo Lee & Junho Byun & Gayong Shim & Yu-Kyoung Oh, 2022. "Fibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29186-8
    DOI: 10.1038/s41467-022-29186-8
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    1. Hongjiao Xu & Qian Zhao & Nazi Song & Zhibin Yan & Runfeng Lin & Shuohan Wu & Lili Jiang & Sihua Hong & Junqiu Xie & Huihao Zhou & Rui Wang & Xianxing Jiang, 2020. "AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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