Albumin mediates PPAR-gamma or C/EBP-alpha-induced phenotypic changes in pancreatic stellate cells.
Activation of quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells is a key event of liver fibrosis, and adipogenic transcription factors, PPAR-gamma and C/EBP-alpha, reverse HSC activation. As albumin was reported to maintain the quiescent phenotype of stellate cells, we examined whether it plays a role in PPAR-gamma and C/EBP-alpha-mediated effects. Pancreatic stellate cells (PSCs) were isolated from rat pancreas and used in their culture-activated phenotype. Forced expression of PPAR-gamma or C/EBP-alpha in PSCs increased albumin mRNA and protein levels by >2.5-fold, which is accompanied with increased C/EBP-beta binding to albumin promoter. PPAR-gamma and C/EBP-alpha 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-gamma and C/EBP-alpha in PSCs and that it can be an attractive molecular target for anti-fibrotic therapies.
Kim
Nayoung
N
Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707, Republic of Korea.
Choi
Soyoung
S
Lim
Chaeseung
C
Lee
Hongsik
H
Oh
Junseo
J
D000418:Albumins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression; D047495:PPAR gamma / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
D000418:Albumins; D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D047495:PPAR gamma; D034741:RNA, Small Interfering