Inhibition of myofibroblastic transformation of cultured rat hepatic stellate cells by methylxanthines and dibutyryl cAMP.
Stellate cells isolated from rat liver and cultured on uncoated plastic plates in serum-containing medium started proliferating and transforming to myofibroblastic cells. However, stellate cells did not proliferate when cultured in the presence of 3-isobutyl-1-methylxanthine or dibutyryl cAMP (dBcAMP). These substances significantly reduced [3h] thymidine incorporation of the proliferating cells. Morphologically, stellate cells cultured in the presence of 3-isobutyl-1-methylxanthine or dibutyryl cAMP kept well-developed processes and lipid droplets while untreated cells exhibited myofibroblastic characteristics. Western blot analysis and immunocytochemical studies revealed that 3-isobutyl-1-methylxanthine and dBcAMP suppressed the expression of alpha-smooth muscle actin in stellate cells. 3-isobutyl-1-methylxanthine increased the cellular levels of cAMP from a basal value of 0.7 +/- 0.1 to 8.5 +/- 1.7 pmol/well in stellate cells. Thus, 3-isobutyl-1-methylxanthine and dBcAMP inhibit the myofibroblastic transformation of stellate cells in vitro in some cAMP-related mechanism.
Kawada
N
N
Department of Internal Medicine III, Osaka City University Medical School, Japan.
Kuroki
T
T
Kobayashi
K
K
Inoue
M
M
Kaneda
K
K
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002461:Cell Line, Transformed; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology*
D014970:Xanthines; D003994:Bucladesine; D013936:Thymidine