Effect of aldosterone on collagen steady state levels in primary and subcultured rat hepatic stellate cells

Background/Aims: Activation of the renin-angiotensin-aldosterone system can lead to collagen accumulation and reactive myocardial fibrosis. This study aims at evaluating the effect of aldosterone on extracellular matrix synth esis by rat hepatic stellate cells. Methods: Cultured cells were treated with different concentrations of aldos terone (10(-6)-10(-10) M) and metabolically labeled with S-35-methionine/S- 35-cysteine. Procollagen types I, III and IV, laminin and fibronectin were specifically immunoprecipitated and quantified by phosphor imaging. Using t he reverse transcription-polymerase chain reaction, we investigated the exp ression of the mineralocorticoid receptor in hepatic stellate cells. Results: Quantitation showed that 10(-6) M aldosterone induced procollagen type I synthesis significantly, whereas procollagen type IV expression was significantly affected by 10(-9) and 10(-10) M aldosterone, both in primary hepatic stellate cells. RT-PCR experiments clearly demonstrated a lack of expression of the mineralocorticoid receptor in hepatic stellate cells. Conclusion: We demonstrated that aldosterone altered moderately procollagen type I and IV synthesis by primary hepatic stellate cells, but not by acti vated stellate cells which are the principal cellular sources of extracellu lar matrix proteins in chronic liver disease. Moreover, hepatic stellate ce lls do not express the mineralocorticoid receptor, suggesting that the obse rved modest changes of extracellular matrix synthesis are probably due to m ineralocorticoid receptor unrelated mechanisms. (C) 2001 European Associati on for the Study of the Liver. Published by Elsevier Science B.V. All right s reserved.