Effects of TGF beta 1 on the proliferation and differentiation of an immortalized astrocyte cell line: relationship with extracellular matrix.

The astrocyte cell line (C.LT.T.1.1.), which is immortalized and has retained a normal density-dependent regulation of growth, is a suitable model for studying the relationships between proliferation, differentiation, and the production of extracellular matrix. The growth factor TGF beta 1 was used to modulate these processes. When added to proliferative cells, it inhibited growth and caused morphological changes. It also suppressed the growth arrest at confluence, so that the cells formed multilayers of parallel spindle-shaped cells. Whereas untreated control cells expressed progressively the glial fibrillary acidic protein (GFAP) after arrest of multiplication, the addition of TGF beta 1 to proliferative cells prevented GFAP expression and accumulation of its mRNA. Concomitantly, it increased the amounts of laminin, fibronectin, and collagens synthesized during the growth phase and greatly altered the composition and the structure of the matrix deposited at confluence. In contrast, when added after cell differentiation had begun, TGF beta 1 did not alter the appearance of the matrix whereas it still stimulated, but to a lesser extent, extracellular matrix components production. The results show that TGF beta 1 prevents the transition from the proliferating to the differentiating state and correlatively alters the composition and structure of the extracellular matrix.