Journal of Clinical Investigation · 1987 · 469 citations · 30 references
Life SciencesCell BiologyMolecular BiologyGene ExpressionSignal TransductionTranscriptional RegulationExtracellular MatrixFibrosisFibrous ProteinsGrowth Factor SignalingProtein SynthesisCollagen Type I SynthesisFibroblast ActivationTransforming Growth Factor Beta Regulation
Transforming growth factor‑β induces rapid fibrosis, chemotaxis, and elevated collagen and fibronectin biosynthesis in fibroblasts. The study aimed to investigate how TGF‑β stimulates collagen and fibronectin synthesis in cultured human foreskin fibroblasts. The authors examined the molecular mechanisms underlying this stimulation. TGF‑β preferentially increased fibronectin and type I procollagen mRNA stability, raising their steady‑state levels 3‑5 fold without altering transcription rates, thereby partially explaining the enhanced synthesis of these proteins.
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.
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Anita B. Roberts, Michael B. Sporn, Richard K. Assoian et al. · Proceedings of the National Academy of Sciences · 1986 · 2.9K citations · Full text
Richard K. Assoian, Akira Komoriya, Chester A. Meyers et al. · Journal of Biological Chemistry · 1983 · 1.6K citations · Full text