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Thymosin β 4 Upregulates the Expression of Hepatocyte Growth Factor and Downregulates the Expression of PDGF‐β Receptor in Human Hepatic Stellate Cells
Author(s) -
BARNAEVA ELENA,
NADEZHDA AGLADZE,
HANNAPPEL EWALD,
SJOGREN MARIA H.,
ROJKIND MARCOS
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1415.035
Subject(s) - hepatic stellate cell , hepatocyte growth factor , matrix metalloproteinase , growth factor , extracellular matrix , fibrosis , hepatocyte , tissue inhibitor of metalloproteinase , cancer research , downregulation and upregulation , microbiology and biotechnology , hepatocyte growth factor receptor , platelet derived growth factor receptor , hepatic fibrosis , biology , chemistry , endocrinology , receptor , medicine , c met , gene , biochemistry , in vitro
: 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 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‐β receptor mRNAs in these cells. Overall, these findings suggest that Tβ 4 has antifibrogenic potential.