PMID- 22266308
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20120206
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 418
IP  - 1
DP  - 2012 Feb 3
TI  - Recombinant fusion protein of albumin-retinol binding protein inactivates 
      stellate cells.
PG  - 191-7
LID - 10.1016/j.bbrc.2012.01.012 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Choi, Soyoung
AU  - Choi S
AD  - Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, 
      Ansan, Gyeonggi do 425-707, Republic of Korea.
FAU - Park, Sangeun
AU  - Park S
FAU - Kim, Suhyun
AU  - Kim S
FAU - Lim, Chaeseung
AU  - Lim C
FAU - Kim, Jungho
AU  - Kim J
FAU - Cha, Dae Ryong
AU  - Cha DR
FAU - Oh, Junseo
AU  - Oh J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120112
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Albumins)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Fats)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinol-Binding Proteins)
SB  - IM
MH  - Albumins/chemistry/genetics/*metabolism
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/metabolism/pharmacology
MH  - Cystic Fibrosis/metabolism/pathology
MH  - Fats/metabolism
MH  - Humans
MH  - Liver Cirrhosis/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Pancreatic Stellate Cells/drug effects/*metabolism/*pathology
MH  - Protein Structure, Tertiary
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Fusion Proteins/chemistry/genetics/*metabolism
MH  - Retinol-Binding Proteins/chemistry/genetics/*metabolism
MH  - Transfection
EDAT- 2012/01/24 06:00
MHDA- 2012/04/10 06:00
CRDT- 2012/01/24 06:00
PHST- 2011/12/09 00:00 [received]
PHST- 2012/01/05 00:00 [accepted]
PHST- 2012/01/24 06:00 [entrez]
PHST- 2012/01/24 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
AID - S0006-291X(12)00035-6 [pii]
AID - 10.1016/j.bbrc.2012.01.012 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Feb 3;418(1):191-7. doi: 
      10.1016/j.bbrc.2012.01.012. Epub 2012 Jan 12.