Ligands of peroxisome proliferator-activated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells.
Gastroenterology
; 119(2): 466-78, 2000 Aug.
Article
in En
| MEDLINE
| ID: mdl-10930382
ABSTRACT
BACKGROUND & AIMS:
Proliferation and migration of hepatic stellate cells (HSCs) and expression of chemokines are involved in the pathogenesis of liver inflammation and fibrogenesis. Peroxisome proliferator-activated receptor (PPAR)-gamma is a receptor transcription factor that controls growth and differentiation in different tissues. We explored the effects of PPAR-gamma agonists on the biological actions of cultured human HSCs.METHODS:
HSCs were isolated from normal human liver tissue and used in their myofibroblast-like phenotype or immediately after isolation. Activation of PPAR-gamma was induced with 15-deoxy-Delta(12, 14)-prostaglandin J(2) or with troglitazone.RESULTS:
PPAR-gamma agonists dose-dependently inhibited HSC proliferation and chemotaxis induced by platelet-derived growth factor. This effect was independent of changes in postreceptor signaling or expression of c-fos and c-myc and was associated with inhibition of cell cycle progression beyond the G(1) phase. Activation of PPAR-gamma also resulted in a complete inhibition of the expression of monocyte chemotactic protein 1 at the gene and protein levels. Comparison of quiescent and culture-activated HSCs revealed a marked decrease in PPAR-gamma expression in activated cells.CONCLUSIONS:
Activation of PPAR-gamma modulates profibrogenic and proinflammatory actions in HSCs. Reduced PPAR-gamma expression may contribute to confer an activated phenotype to HSCs.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Receptors, Cytoplasmic and Nuclear
/
Thiazolidinediones
/
Hepatitis
/
Liver
/
Liver Cirrhosis
Language:
En
Journal:
Gastroenterology
Year:
2000
Type:
Article
Affiliation country:
Italy