[Inhibition of the activation and collagen production of cultured rat hepatic stellate cells by antisense oligonucleotides against transforming growth factor-beta 1].
In order to investigate whether the antisense oligonucleotides (ASON) against TGF beta 1 inhibit the activation and collagen production of cultured rat hepatic stellate cells, the authors synthesized two 20-mer phosphorothioate antisense oligonucleotides and their sense or missense oligonucleotides, and then treated the rat hepatic stellate cells (HSC) with these oligonucleotides at different concentrations respectively. HSC activation was assessed by the expression of alpha-smooth muscle actin (alpha-SMA), and TGF beta 1 level was determined by a standard bioassay. The production of collagen was measured by the incorporation of 3H-Proline into cultured rat HSCs. The results showed that the ASON against the translation initiation region of TGF beta 1 at a final concentration of 10 mumol/L could inhibit the HSCs activation, the secretion of TGF beta 1 and the production of collagen in HSCs significantly (P < 0.05), whereas the controls (sense or missense oligonucleotides) had no effect at the same concentration. All of the oligonucleotides had no cytoxicity to HSCs. These findings suggested that TGF beta 1 ASON might be useful for the treatment of hepatic fibrosis.
Liu
X
X
Department of Internal Medicine, First Affiliated Hospital, WCUMS, Chengdu 610041.
Yang
L
L
Chen
D
D
Zhang
Z
Z
Qiang
O
O
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D000199:Actins; D016376:Oligonucleotides, Antisense; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen