Release and activation of platelet latent TGF–β in blood clots during dissolution with plasmin

Abstract

Transforming growth factor β1 (TGF–β1) is a platelet–derived cytokine involved in both normal wound healing and scarring. We show that human platelets contain two pools of latent TGF–β1, which constitute more than 95% of the total TGF–β assayed in whole platelets. During clotting, one pool, the large latent TGF–β complex consisting of latent TGF–β binding protein (LTBP), the latency–associated peptide (LAP) and the 25–kD mature TGF–β1 dimer is released into the serum. A second pool, which contains LAP but not LTBP, is retained in the clot, but can be released by RGD peptide. When the clot is dissolved by plasmin this bound TGF–β1 is gradually activated and released. If similar mechanisms operate in vivo, the clot will act as a slow–release capsule of TGF–β1 activity during wound healing.

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Grainger, D., Wakefield, L., Bethell, H. et al. Release and activation of platelet latent TGF–β in blood clots during dissolution with plasmin. Nat Med 1, 932–937 (1995). https://doi.org/10.1038/nm0995-932

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