G proteins are involved in the suppression of collagen alpha 1 (I) gene expression in cultured rat hepatic stellate cells.
We analyse the role of the G proteins in regulating collagen gene expression by measuring collagen alpha 1(I) mRNA levels in cultured hepatic stellate cells in basal conditions and after stimulating or inhibiting the major intracellular signalling pathways. Stimulation of Gs protein and adenylyl cyclase or the addition of 8Br-cAMP to the cells led to a decrease in collagen alpha 1(I) mRNA levels, while blocking protein kinase A abolished this effect. Blocking Gi protein, phospholipase A2 and C, calcium channels and calmodulin resulted in a significant increase in collagen mRNA levels. PKC stimulation led to a marked decrease in these levels. These results suggest that collagen gene expression is inhibited by a number of intracellular pathways. A Gs and a pertussis toxin-sensitive G protein seem to initiate cellular response. Transcription factors, acting in these pathways, must be identified. However, it seems that they do not need to be synthesised.
Solís-Herruzo
J A
JA
Gastroenterología, Centro de Investigación, Hospital Universitario Doce de Octubre, Universidad Complutense, Madrid, Spain. jasolis@h12o.es
Hernández
I
I
De la Torre
P
P
García
I
I
Sánchez
J A
JA
Fernández
I
I
Castellano
G
G
Muñoz-Yagüe
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D003094:Collagen / Q000235:genetics*; D000242:Cyclic AMP / Q000032:analysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D007295:Inositol Phosphates / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D012333:RNA, Messenger; D003094:Collagen; D002772:Cholera Toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D002118:Calcium