Albumin inhibits the nuclear translocation of Smad3 via interleukin-1beta signaling in hepatic stellate cells
- Authors
- Park, Ji Hoon; Kim, Janghyun; Choi, So-Young; Lee, Boram; Lee, Jung-Eun; Park, Heekyung; Moon, Ji Wook; Park, Sun-Hwa; Lee, Jae Min; Lee, Hong Sik; Oh, Junseo
- Issue Date
- 4-2월-2021
- Publisher
- NATURE RESEARCH
- Citation
- SCIENTIFIC REPORTS, v.11, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 11
- Number
- 1
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/49608
- DOI
- 10.1038/s41598-021-82758-4
- ISSN
- 2045-2322
- Abstract
- Activation of quiescent hepatic stellate cells (HSCs) to myofibroblasts plays a key role in liver fibrosis. We had previously shown that albumin and its derivative, R-III (a retinol-binding protein-albumin domain III fusion protein), inhibited HSC activation by sequestering retinoic acid (RA) and that R-III administration reduced carbon tetrachloride (CCl4)-induced liver fibrosis. In this study, we aimed to elucidate the mechanism of action of albumin downstream of RA sequestration. Nuclear factor-kappa B p65 was evenly distributed in the cytoplasm in activated mouse HSCs, whereas albumin expression or R-III treatment (albumin/R-III) caused the nuclear translocation of p65, probably via RA sequestration, resulting in a dramatic increase in interleukin-1beta (IL-1 beta) expression. Albumin/R-III in turn induced the phosphorylation of Smad3 at the linker region, inhibiting its nuclear import in an IL-1 beta -dependent manner. Consistent with the in vitro results, the level of IL-1 beta mRNA expression was higher in CCl4/R-III-treated livers than in CCl4-treated livers. These findings reveal that albumin/R-III inhibits the transforming growth factor-beta -Smad3 signaling as well as the retinoic acid receptor-mediated pathway, which probably contributes to the inhibition of HSC activation, and suggest that R-III may be an anti-fibrotic drug candidate.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
- College of Medicine > Department of Medical Science > 1. Journal Articles
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