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

Authors
Lee, JaiwooByun, JunhoShim, GayongOh, Yu-Kyoung
Issue Date
21-Mar-2022
Publisher
NATURE PORTFOLIO
Citation
NATURE COMMUNICATIONS, v.13, no.1
Journal Title
NATURE COMMUNICATIONS
Volume
13
Number
1
URI
http://scholarworks.bwise.kr/ssu/handle/2018.sw.ssu/42126
DOI
10.1038/s41467-022-29186-8
ISSN
2041-1723
Abstract
In liver fibrosis, activated hepatic stellate cells are known to overexpress fibroblast activation protein. Here we report a targeted anti-fibrotic 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.
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