[Inhibition of the activation and collagen production of cultured rat hepatic stellate cells by antisense oligonucleotides against transforming growth factor-beta 1 is enhanced by cationic liposome delivery].
In order to investigate the inhibition of the activation and collagen production of cultured rat hepatic stellate cells (HSC) by antisense oligonucleotides (ASON) against TGF beta 1 after cationic liposome (lipofectin) delivery, the authors synthesized a 20-mer phosphorothioate antisense oligonucleotide of TGF beta 1 mRNA, and its sense of missense oligonucleotides, and then treated the HSC with cationic liposome/oligonucleotide complexes respectively. The cellular uptake of 32P-labelled oligonucleotides was determined by liquid scintillation counting, and HSC activation was assessed by the expression of alpha-smooth muscle actin(alpha-SMA). The cellular uptake of lipofectin/32P-ASON complex was approximately five-fold higher than that of 32P-ASON alone. Cationic liposome (lipofectin) delivery significantly increased the inhibition of HSCs activation by ASON, while compared with the use of naked TGF beta 1 ASON at the same concentration (at a final concentration of 1 mumol/L, P < 0.05). However, these effects were not observed in lipofectin alone, liposome/sense or missense oligos complexes at the same concentration. The oligonucleotide or lipofectin/oligos complexes had no cytotoxicity to rat HSCs in culture. These findings suggest that cationic liposome is an effective vehicle to improve the delivery of ASON to rat HSCs in culture, and the cationic liposome/TGF beta 1 ASON complex may be useful for the treatment of hepatic fibrosis.
Liu
X
X
Department of Internal Medicine, First Affiliated Hospital, WCUMS, Chengdu 610041.
Zhang
Z
Z
Yang
L
L
Chen
D
D
Wang
Y
Y
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D002412:Cations; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D022781:Hepatocytes / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage; D008103:Liver Cirrhosis / Q000628:therapy; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D000199:Actins; D002412:Cations; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D010714:Phosphatidylethanolamines; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C020888:1,2-dielaidoylphosphatidylethanolamine; D003094:Collagen