TY - JOUR
T1 - Albumin mediates PPAR-γ or C/EBP-α-induced phenotypic changes in pancreatic stellate cells
AU - Kim, Nayoung
AU - Choi, Soyoung
AU - Lim, Chaeseung
AU - Lee, Hongsik
AU - Oh, Junseo
N1 - Funding Information:
We thank Ho Kim and Kyunghee Noh for technical assistance. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. 2009-0076453 ).
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Activation of quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells is a key event of liver fibrosis, and adipogenic transcription factors, PPAR-γ and C/EBP-α, reverse HSC activation. As albumin was reported to maintain the quiescent phenotype of stellate cells, we examined whether it plays a role in PPAR-γ and C/EBP-α-mediated effects. Pancreatic stellate cells (PSCs) were isolated from rat pancreas and used in their culture-activated phenotype. Forced expression of PPAR-γ or C/EBP-α in PSCs increased albumin mRNA and protein levels by >2.5-fold, which is accompanied with increased C/EBP-β binding to albumin promoter. PPAR-γ and C/EBP-α also induced a phenotypic switch from activated to quiescent cells and, interestingly, suppression of albumin using short-hairpin RNA (shRNA) blocked their effects. Therefore, our findings suggest that albumin may be a downstream effector of PPAR-γ and C/EBP-α in PSCs and that it can be an attractive molecular target for anti-fibrotic therapies.
AB - Activation of quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells is a key event of liver fibrosis, and adipogenic transcription factors, PPAR-γ and C/EBP-α, reverse HSC activation. As albumin was reported to maintain the quiescent phenotype of stellate cells, we examined whether it plays a role in PPAR-γ and C/EBP-α-mediated effects. Pancreatic stellate cells (PSCs) were isolated from rat pancreas and used in their culture-activated phenotype. Forced expression of PPAR-γ or C/EBP-α in PSCs increased albumin mRNA and protein levels by >2.5-fold, which is accompanied with increased C/EBP-β binding to albumin promoter. PPAR-γ and C/EBP-α also induced a phenotypic switch from activated to quiescent cells and, interestingly, suppression of albumin using short-hairpin RNA (shRNA) blocked their effects. Therefore, our findings suggest that albumin may be a downstream effector of PPAR-γ and C/EBP-α in PSCs and that it can be an attractive molecular target for anti-fibrotic therapies.
KW - Albumin
KW - Fibrosis
KW - Lipid droplet formation
KW - PPAR-γ
KW - Pancreatic stellate cells
UR - http://www.scopus.com/inward/record.url?scp=72949104130&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.11.112
DO - 10.1016/j.bbrc.2009.11.112
M3 - Article
C2 - 19932685
AN - SCOPUS:72949104130
SN - 0006-291X
VL - 391
SP - 640
EP - 644
JO - Biochemical and biophysical research communications
JF - Biochemical and biophysical research communications
IS - 1
ER -