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

Hong Sik Lee, Hyeyeun Jeong, Sangeun Park, Wonbaek Yoo, Soyoung Choi, Kyungmin Choi, Min-Goo Lee, Mihwa Lee, Dae-Ryong Cha, Young Sik Kim, Jeeyoung Han, Wonkon Kim, Sun-Hwa Park, Jun Seo Oh

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 CCl<inf>4</inf>- and bile duct ligation-induced liver fibrosis. R-III also exhibited a preventive effect against CCl<inf>4</inf>-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.

Original languageEnglish
Pages (from-to)819-830
Number of pages12
JournalEMBO Molecular Medicine
Volume7
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

Keywords

  • Albumin
  • Anti-fibrotic drug
  • Fibrosis
  • Hepatic stellate cell
  • Retinoic acid

ASJC Scopus subject areas

  • Molecular Medicine

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