Fusion protein of retinol-binding protein and albumin domain III reduces liver fibrosis
- Authors
- Lee, Hongsik; Jeong, Hyeyeun; Park, Sangeun; Yoo, Wonbaek; Choi, Soyoung; Choi, Kyungmin; Lee, Min-Goo; Lee, Mihwa; Cha, DaeRyong; Kim, Young-Sik; Han, Jeeyoung; Kim, Wonkon; Park, Sun-Hwa; Oh, Junseo
- Issue Date
- 6월-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
- Indexed
- SCIE
SCOPUS
- Journal Title
- EMBO MOLECULAR MEDICINE
- Volume
- 7
- Number
- 6
- Start Page
- 819
- End Page
- 830
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/93464
- DOI
- 10.15252/emmm.201404527
- ISSN
- 1757-4676
- 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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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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