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


METHODS
Cultured cells were treated with different concentrations of aldosterone (10(-6)-10(-10) M) and metabolically labeled with 35S-methionine/35S-cysteine. Procollagen types I, III and IV, laminin and fibronectin were specifically immunoprecipitated and quantified by phosphor imaging. Using the reverse transcription-polymerase chain reaction, we investigated the expression 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.


CONCLUSIONS
We demonstrated that aldosterone altered moderately procollagen type I and IV synthesis by primary hepatic stellate cells, but not by activated stellate cells which are the principal cellular sources of extracellular matrix proteins in chronic liver disease. Moreover, hepatic stellate cells do not express the mineralocorticoid receptor, suggesting that the observed modest changes of extracellular matrix synthesis are probably due to mineralocorticoid receptor unrelated mechanisms.
Laboratory for Molecular Liver Cell Biology, Faculty of Medicine and Pharmacy, Free University of Brussels (VUB), Jette, Belgium. krom@cyto.vub.ac.be
K
K
Rombouts
T
T
Niki
A
A
Wielant
K
K
Hellemans
D
D
Schuppan
N
N
Kormoss
A
A
Geerts
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects
D005353:Fibronectins; D007797:Laminin; D011347:Procollagen; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003094:Collagen