Jorma Keski-Oja

Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts.

Transforming growth factor-beta (TGF beta), when injected subcutaneously into newborn mice, induces a rapid fibrotic response, stimulates chemotaxis, and elevates the rates of biosynthesis of collagen and fibronectin by fibroblasts in vitro. We explored the molecular mechanisms of TGF beta-mediated stimulation of collagen and fibronectin synthesis in cultured human foreskin fibroblasts. TGF beta preferentially stimulated the synthesis of fibronectin and type I procollagen chains 3-5-fold as shown by polypeptide analysis. Concomitant elevation in the steady state levels of messenger RNAs (mRNAs) coding for type I procollagen and fibronectin also occurred but without a net increase in the rate of transcription of either of these genes. The preferential stabilization of mRNAs specifying type I procollagen and fibronectin provides a partial explanation for the mechanisms by which TGF beta enhances the synthesis of type I procollagen and fibronectin in mesenchymal cells.

Transforming Growth Factors in the Regulation of Malignant Cell Growth and Invasion

AbstractINTRODUCTION The interactions between cells and their extracellular matrices are controlled by various intracellular and exogenous signals. The control of these interactions by polypeptide growth factors appears to involve different levels of regulation. Growth factors can, in addition to the regulation of cell proliferation, direct cell migration and movement, alter the production of different connective tissue components, and regulate extracellular proteolysis. Of particular interest are the autocrine and paracrine growth factors produced by both normal and malignant cells (1-5).