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Inhibition of myofibroblastic transformation of cultured rat hepatic stellate cells by methylxanthines and dibutyryl cAMP

Digestive Diseases and Sciences, ISSN: 0163-2116, Vol: 41, Issue: 5, Page: 1022-1029
1996
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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 [H]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 α-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.

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