albumin - publications

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1. Biochem Biophys Res Commun. 2012 Jan 12. [Epub ahead of print]

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

Choi S, Park S, Kim S, Lim C, Kim J, Cha DR, Oh J.

Laboratory of Cellular Oncology, Korea University Graduate School of Medicine,
Ansan, Gyeonggi do 425-707, Republic of Korea.

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(domain III) (R-III) and albumin(domain 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.

Copyright © 2012. Published by Elsevier Inc.

PMID: 22266308 [PubMed - as supplied by publisher]