Thymosin beta4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF-beta receptor in human hepatic stellate cells.
Hepatic stellate cells (HSCs) are the main producers of type I collagen in the liver, and therefore are responsible, in part, for the fibrous scar observed in cirrhotic livers. Although there is no approved treatment for this deadly disease, drugs inducing HSC apoptosis in animals (gliotoxin) and hepatocyte regeneration in man (hepatocyte growth factor [HGF]), have been used successfully in ameliorating liver fibrosis. In this communication we investigated whether thymosin beta(4) (Tbeta(4)), an actin-sequestering peptide that prevents scarring of the heart after a myocardial infarction and that prevents kidney fibrosis in animals, has the potential to be used to treat liver fibrosis. To this end we studied whether the administration of Tbeta(4) to HSCs could alter the expression of genes encoding for extracellular matrix components, as well as those required for differentiation of HSCs. Our preliminary findings show that Tbeta(4) had no effect on the expression of alpha2 (I) collagen, tissue inhibitor of metalloproteinases-1, and matrix metalloproteinase-2 mRNAs. However, it upregulated the expression of HGF and downregulated the expression of platelet-derived growth factor-beta receptor mRNAs in these cells. Overall, these findings suggest that Tbeta(4) has antifibrogenic potential.
Barnaeva
Elena
E
Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC, USA.
Nadezhda
Agladze
A
Hannappel
Ewald
E
Sjogren
Maria H
MH
Rojkind
Marcos
M
D002454:Cell Differentiation; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D013947:Thymosin / Q000494:pharmacology*; D000099201:Thymosin beta(4)
D017931:DNA Primers; D005343:Fibrinolytic Agents; D017228:Hepatocyte Growth Factor; D012333:RNA, Messenger; D020797:Receptor, Platelet-Derived Growth Factor beta; D013947:Thymosin; D000099201:Thymosin beta(4)