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Title 

Fusion protein of retinol-binding protein and albumin domain III reduces liver fibrosis

Authors 

H LeeH JeongS ParkW YooS ChoiK ChoiM G LeeM LeeD R ChaY S KimJ HanWon Kon KimS H ParkJ Oh

Publisher 

Wiley Open Access

Issue Date 

2015

Citation 

EMBO Molecular Medicine, vol. 7, no. 6, pp. 819-830

Keywords 

AlbuminAnti-fibrotic drugFibrosisHepatic stellate cellRetinoic acid

Abstract 

Activated hepatic stellate cells (HSCs) play a key role in liver fibrosis, and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin and its derivative designed for stellate cell-targeting, retinol-binding protein-albumin domain III fusion protein (referred to as R-III), inactivate cultured HSCs. Here, we investigated the mechanism of action of albumin/R-III in HSCs and examined the anti-fibrotic potential of R-III in vivo. R-III treatment and albumin expression downregulated retinoic acid (RA) signaling which was involved in HSC activation. RA receptor agonist and retinaldehyde dehydrogenase overexpression abolished the anti-fibrotic effect of R-III and albumin, respectively. R-III uptake into cultured HSCs was significantly decreased by siRNA-STRA6, and injected R-III was localized predominantly in HSCs in liver. Importantly, R-III administration reduced CCl4- and bile duct ligation-induced liver fibrosis. R-III also exhibited a preventive effect against CCl4-inducd liver fibrosis. These findings suggest that the anti-fibrotic effect of albumin/R-III is, at least in part, mediated by downregulation of RA signaling and that R-III is a good candidate as a novel anti-fibrotic drug.

ISSN 

1757-4676

Link 

http://dx.doi.org/10.15252/emmm.201404527

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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