Thymosin β_4 Upregulates the Expression of Hepatocyte Growth Factor and Downregulates the Expression of PDGF-β Receptor in Human Hepatic Stellate Cells

摘要

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 clrrhotic 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 fibro-sis. In this communication we investigated whether thymosin β_4 (Tβ_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 Tβ_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 Tβ_4 had no effect on the expression of α2 (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-P receptor mRNAs in these cells. Overall, these findings suggest that Tβ_4 has antifibrogenic potential.