Kawada N, Kuroki T, Kobayashi K, Inoue M, Kaneda K
Department of Internal Medicine III, Osaka City University Medical School, Japan.
Dig Dis Sci. 1996 May;41(5):1022-9. doi: 10.1007/BF02091547.
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.