Synthesis of cellular fibronectin by rat liver fat-storing (Ito) cells: regulation by cytokines.

Fibronectins are multifunctional extracellular matrix glycoproteins that seem to play a pacemaker role in liver fibrogenesis. The expression of cellular fibronectin by rat liver fat-storing cells in primary culture and their modulation by cytokines was studied. Cellular fibronectin was localized in the cytoplasm and on the surface of cultured fat-storing cells as well as in extracellular matrix fibrils by indirect immunofluorescence. Immunoprecipitation of endogenously labeled fibronectin using type specific antibodies showed the synthesis and secretion of cellular fibronectin by fat-storing cells in vitro. ED1 positive sequences specific for cellular fibronectin and absent in plasma fibronectin were detected within the total RNA of fat-storing cells. Cellular fibronectin synthesis was severalfold enhanced in "activated" vs. "resting" fat-storing cells. Treatment of fat-storing cells with transforming growth factor beta 1 resulted in a dose dependent increase of fibronectin synthesis. In contrast, interferon gamma inhibited the synthesis of fibronectin. The stimulation of fibronectin synthesis by transforming growth factor beta 1 and the inhibition by interferon gamma might be of importance for pathophysiology and therapy of liver fibrogenesis.