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

Rajendra Raghow, Arnold E. Postlethwaite, Jorma Keski‐Oja, Harold L. Moses, A H Kang

Journal of Clinical Investigation · 1987 · 469 citations · 30 references

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TL;DR

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.

Abstract

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.

References

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