Post-translational activation of TGF-.beta..sub.1 involving the

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060903678

ABSTRACT:
A protein called transforming growth factor-beta (TGF-.beta.) is important in causing the inflammation and progressive scar tissue in pulmonary fibrosis. The TGF-.beta..sub.1 isoform is important in the pathogenesis of pulmonary fibrosis. It is usually secreted non-covalently bound to a latency associated peptide (LAP) which renders it biologically inactive. The inactive form is called latent TGF-.beta..sub.1 (L-TGF-.beta..sub.1). Activation of L-TGF-.beta..sub.1 involves L-TGF-.beta..sub.1 /TSP-1 complex which interacts with the TSP-1 receptor, CD36, to process L-TGF-.beta..sub.1 to the mature form in the presence of plasmin. Synthetic or natural CD36 peptides or fragments thereof can be used to prevent activation of TGF-.beta..sub.1, in mammalian alveolar macrophages, thereby controlling the inflammation process.

REFERENCES:
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Khalil et al, post-translational activation of TGF-B1 by rat alveolar macrophages requires plasmin, thrombospondin and TSp-1 receptor, CD36, American Journal of Respiratory and critical care medicine, 1995 international Conference, abstract, 1995.
Stacey Schultz et al. "Thrombospondin Causes Activation of Latent Transforming Growth Factor-.beta. Secreted by Endothelial Cells by a Novel Mechanism", The Journal of Cell Biology, vol. 122, No. 4, Aug. 1993, p923-932.
N. Khalil, et al, "Post-Translational Activation of TGF-B, etc." American Journal of Respiratory and Critical Care Medicine, vol. 151, No. 4, Apr. 1995.

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