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Recombinant fusion protein of albumin-retinol binding protein inactivates stellate cells

Authors
Choi, SoyoungPark, SangeunKim, SuhyunLim, ChaeseungKim, JunghoCha, Dae RyongOh, Junseo
Issue Date
3-Feb-2012
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
Albumins; Retinol-binding protein; Fibrosis; Pancreatic stellate cells; Anti-fibrotic drug
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.418, no.1, pp 191 - 197
Pages
7
Indexed
SCI
SCIE
SCOPUS
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume
418
Number
1
Start Page
191
End Page
197
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/133869
DOI
10.1016/j.bbrc.2012.01.012
ISSN
0006-291X
1090-2104
Abstract
Quiescent pancreatic- (PSCs) and hepatic- (HSCs) stellate cells store vitamin A (retinol) in lipid droplets via retinol binding protein (RBP) receptor and, when activated by profibrogenic stimuli, they transform into myofibroblast-like cells which play a key role in the fibrogenesis. Despite extensive investigations, there is, however, currently no appropriate therapy available for tissue fibrosis. We previously showed that the expression of albumin, composed of three homologous domains (I-III), inhibits stellate cell activation, which requires its high-affinity fatty acid-binding sites asymmetrically distributed in domain I and III. To attain stellate cell-specific uptake, albumin (domain I/III) was coupled to RBP; RBP-albumin(domainIII) (R-III) and albumin(damain) (I) -RBP-albumin(III) (I-R-III). To assess the biological activity of fusion proteins, cultured PSCs were used. Like wild type albumin, expression of R-III or I-R-III in PSCs after passage 2 (activated PSCs) induced phenotypic reversal from activated to fat-storing cells. On the other hand, R-III and I-R-III, but not albumin, secreted from transfected 293 cells were successfully internalized into and inactivated PSCs. FPLC-purified R-III was found to be internalized into PSCs via caveolae-mediated endocytosis, and its efficient cellular uptake was also observed in HSCs and podocytes among several cell lines tested. Moreover, tissue distribution of intravenously injected R-III was closely similar to that of RBP. Therefore, our data suggest that albumin-RBP fusion protein comprises of stellate cell inactivation-inducing moiety and targeting moiety, which may lead to the development of effective anti-fibrotic drug. (C) 2012 Elsevier Inc. All rights reserved.
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