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Cited 22 time in webofscience Cited 25 time in scopus
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Fusion protein of retinol-binding protein and albumin domain III reduces liver fibrosis

Authors
Lee, HongsikJeong, HyeyeunPark, SangeunYoo, WonbaekChoi, SoyoungChoi, KyungminLee, Min-GooLee, MihwaCha, DaeRyongKim, Young-SikHan, JeeyoungKim, WonkonPark, Sun-HwaOh, Junseo
Issue Date
Jun-2015
Publisher
WILEY
Keywords
albumin; anti-fibrotic drug; fibrosis; hepatic stellate cell; retinoic acid
Citation
EMBO MOLECULAR MEDICINE, v.7, no.6, pp 819 - 830
Pages
12
Indexed
SCIE
SCOPUS
Journal Title
EMBO MOLECULAR MEDICINE
Volume
7
Number
6
Start Page
819
End Page
830
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/7858
DOI
10.15252/emmm.201404527
ISSN
1757-4676
1757-4684
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.
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3. Graduate School > Biomedical Research Center > 1. Journal Articles
1. Basic Science > Department of Anatomy > 1. Journal Articles
2. Clinical Science > Department of Pathology > 1. Journal Articles
2. Clinical Science > Department of Nephrology and Hypertension > 1. Journal Articles
1. Basic Science > Department of Physiology > 1. Journal Articles
2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles

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