The Dependence of Transforming Growth Factor-β-Induced Collagen Production on Autocrine Factor Activin A in Hepatic Stellate Cells

• Published in: Endocrinology (Philadelphia) Vol. 145; no. 6; pp. 2753 - 2759
• Main Authors: Wada, Wataru, Kuwano, Hiroyuki, Hasegawa, Yoshihisa, Kojima, Itaru
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.06.2004
• Subjects: Activin Receptors, Type I - metabolism; Activin Receptors, Type II - genetics; Activin Receptors, Type II - metabolism; Activins - metabolism; Activins - pharmacology; Activins - physiology; Animals; Biological and medical sciences; Cells, Cultured; Collagen - biosynthesis; Follistatin - pharmacology; Fundamental and applied biological sciences. Psychology; Genes, Dominant; Hepatocytes - metabolism; Humans; Inhibin-beta Subunits - metabolism; Inhibin-beta Subunits - pharmacology; Inhibin-beta Subunits - physiology; Proteins; Rats; Recombinant Proteins - pharmacology; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; Transforming Growth Factor beta - physiology; Vertebrates: endocrinology; Activin A; Digestive system; Transforming growth factor β; Collagen; Liver; Glycoprotein; Dependence
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2003-1663

The present study was conducted to examine the role of activin A in the activation of cultured rat hepatic stellate cells (HSC). HSC expressed mRNA for the βA-subunit of activin and the type I and II activin receptors. TGF-β increased the mRNA expression of the βA-subunit of activin as well as the release of the βA dimer, activin A. Exogenous activin A activated HSC and increased the expression of α-smooth muscle actin and collagen. Exogenous follistatin, an antagonist of activin A, blocked not only the effect of activin A but also the effect of TGF-β on the expression of type I collagen. Similarly, follistatin inhibited TGF-β-induced secretion of collagen from HSC. Additionally, the effect of TGF-β was markedly reduced in HSC overexpressing the dominant-negative type II activin receptor. In contrast, the effect of activin A on the collagen production was not affected in HSC overexpressing the dominant-negative type II TGF-β receptor. In conclusion, an autocrine factor activin A mediates part of the action of TGF-β on the production of collagen in HSC. The results also suggest that follistatin may be useful for the treatment of hepatic fibrosis.