REGULATION OF EXTRACELLULAR-MATRIX SYNTHESIS BY TRANSFORMING GROWTH FACTOR-BETA(1) IN HUMAN FAT-STORING CELLS

Background: Fat storing cells (FSC) are nonparenchymal liver cells generally considered the major source of the hepatic extracellular matrix (ECM). Transforming growth factor β1 (TGF-β1) is a potent regulator of ECM synthesis in various cell types. In this study, the effect of TGF-β1 on procollagen types I, III, IV, laminin (Lam), and flbronectin (FN) synthesis in cultured human FSCs was analyzed. Methods: FSCs were isolated from wedge sections of normal human livers. Morphological studies were performed by immunofluorescence and electron microscopy. ECM components in human FSC cultures were measured by an enzyme-linked immunosorbent assay. The expression of messenger RNA (mRNA) was evaluated by Northern blot and in situ hybridization. Results: Cultured human FSCs displayed numerous fat droplets in the perinuclear zone, and immunoreactivity for vimentin and α-smooth muscle actin. A weak nonfibrillar staining was observed by using a polyclonal antidesmin antibody. TGF-β1 induced a dose-dependent increase of procollagen I, III, and FN accumulation in human FSC cultures, whereas procollagen IV and Lam production was not affected. Furthermore, TGF-β1 increased the expression of α1(I), α1(III) procollagen, FN and TGF-β1 mRNA in human FSC cultures. Conclusions: These data indicate that TGF-β1 is able to increase the synthesis of procollagen I, III, and FN in cultured human FSCs. Moreover, TGF-β1 can induce its own mRNA in the same cells. © 1993.