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To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1196/annals.1415.035 Byline: ELENA BARNAEVA (a), AGLADZE NADEZHDA (b), EWALD HANNAPPEL (c), MARIA H. SJOGREN (a), MARCOS ROJKIND (b) Keywords: hepatic stellate cells; thymosin [beta]; liver fibrosis; antifibrogenic therapy; PDGF-[beta]; receptor; hepatocyte growth factor Abstract: Abstract: 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].sub.4 (T[beta].sub.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 T[beta].sub.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 T[beta].sub.4 had no effect on the expression of [alpha]2 (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 T[beta].sub.4 has antifibrogenic potential. Author Affiliation: (a)Department of Clinical Investigation, Walter Reed Army Medical Center, Washington DC, USA (b)Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington DC, USA (c)Department of Biochemistry, University of Erlangen, Nuremberg, Erlangen, Germany Article note: Address for correspondence: Marcos Rojkind, M.D., Ph.D., Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Ross Hall 522, 2300 I Street, NW, Washington DC, 20037. Voice: 202-994-2789; fax: 202-994-8974., bcmmmr@gwumc.edu