Plasminogen activator inhibitor type-1 synthesis and mRNA expression in HepG2 cells are regulated by VLDL.
The effect of VLDL on plasminogen activator inhibitor type 1 biosynthesis in HepG2 cells was investigated. Exposure of HepG2 cells to VLDL (range, 10 to 100 micrograms protein per milliliter) for 16 hours resulted in an enhanced release of PAI-1 antigen and PAI activity into conditioned medium, accompanied by the accumulation of intracellular triglycerides. By using a monoclonal antibody (IgG C7) specific to the LDL receptor, we showed that the effect of VLDL is mediated by its interaction with the LDL receptor. Enhanced PAI-1 release was due to increased biosynthesis: PAI-1 mRNA was doubled, mainly because of the effect on the 2.2-kb PAI-1 mRNA rather than the 3.2-kb transcript. Addition of insulin with the VLDL further enhanced PAI-1 antigen release and PAI-1 mRNA accumulation. The effect of VLDL on steady state levels of PAI-1 mRNA was apparently not due to an increase of gene transcription but to stabilization of both PAI-1 mRNA transcripts. The enhancing effect of VLDL on PAI-1 biosynthesis in HepG2 cells may raise PAI-1 antigen levels not only in hypertriglyceridemic states but also in those conditions in which both insulin and VLDL are elevated.
Sironi
L
L
Institute of Pharmacological Sciences and E. Grossi Paoletti Center, University of Milan, Italy.
Mussoni
L
L
Prati
L
L
Baldassarre
D
D
Camera
M
M
Banfi
C
C
Tremoli
E
E
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D017077:Culture Media, Conditioned; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008079:Lipoproteins, VLDL / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011973:Receptors, LDL / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D008079:Lipoproteins, VLDL; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides