Pigment epithelium-derived factor is an angiogenesis and lipid regulator that activates peroxisome proliferator-activated receptor alpha. Adv Exp Med Biol 2008;617:591-7
Date
05/24/2008Pubmed ID
18497086DOI
10.1007/978-0-387-69080-3_61Scopus ID
2-s2.0-46749149713 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
Pigment epithelium-derived factor (PEDF) is an endogenous antiangiogenic protein that also possesses antitumor activity. The mechanisms by which PEDF exerts its actions remains poorly understood. We sought to understand the role of PEDF in hepatocellular carcinoma (HCC), a hypervascular malignancy that has been shown to upregulate enzymes involved in fatty acid synthesis. PEDF expression occurs in two HCC cell lines and is oxygen dependent. Migration studies confirm PEDF's role as an endogenous inhibitor of angiogenesis in HCC cells. Loss of PEDF in an animal model leads to hepatocyte lipid accumulation, proliferation, and cellular atypia. To investigate potential interactions with transcription factors that are involved in fatty acid metabolism and cellular proliferation, we examined PEDF's interaction with PPARalpha in vitro and its functional activity through transactivation assays. We show that PEDF binds to PPARalpha but minimally to PPARgamma. In the presence of the ligand, ciprofibrate, PEDF binding to PPARalpha decreases whereas the presence of troglitazone does not alter PEDF interactions with PPARgamma. Transfection of the PEDF gene in the presence of the PPARalpha/RXR heterodimer demonstrates transcriptional activation of PPARalpha by PEDF. These data show that PEDF regulates lipid metabolism through activation of the transcription factor PPARalpha.
Author List
Chung C, Doll JA, Stellmach VM, Gonzales J, Surapureddi S, Cornwell M, Reddy JK, Crawford SEAuthor
Jennifer A. Doll PhD Assistant Professor in the Biomedical Sciences department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
Carcinoma, HepatocellularCell Hypoxia
Cell Movement
Chromans
Clofibric Acid
Endothelium, Vascular
Eye Proteins
Fibric Acids
Humans
Hypoglycemic Agents
Hypolipidemic Agents
Lipid Metabolism
Liver Neoplasms
Neovascularization, Pathologic
Nerve Growth Factors
PPAR alpha
PPAR gamma
Serpins
Thiazolidinediones
Tumor Cells, Cultured
