Abstract: The present disclosure relates to compounds, compositions and methods for the treatment of diseases through inhibiting the activity of the transforming growth factor beta (TGF-?). More specifically, the disclosed compounds, compositions and methods are useful in the treatment of certain cancers (e.g. multiple myeloma, hematologic malignancies), diseases associated with excessive TGF-? activity including fibrosis, dermal scarring, immune dysfunction, and bone loss by inhibiting the conversion of latent TGF-? to active TGF-?. A method of preventing the activation of TGF-? in pathology is also provided, comprising administering an amount of the compounds sufficient to inhibit conversion of latent TGF-? to active TGF-? by thrombospondin1 (TSP1), resulting in reduced TGF-? activity and reduced adverse effects such as fibrosis, bone loss, and immune dysfunction.

Abstract: The present disclosure relates to compounds, compositions and methods for the treatment of diseases through inhibiting the activity of the transforming growth factor beta (TGF-?). More specifically, the disclosed compounds, compositions and methods are useful in the treatment of certain cancers (e.g. multiple myeloma, hematologic malignancies), diseases associated with excessive TGF-? activity including fibrosis, dermal scarring, immune dysfunction, and bone loss by inhibiting the conversion of latent TGF-? to active TGF-?. A method of preventing the activation of TGF-? in pathology is also provided, comprising administering an amount of the compounds sufficient to inhibit conversion of latent TGF-? to active TGF-? by thrombospondinl (TSP1), resulting in reduced TGF-? activity and reduced adverse effects such as fibrosis, bone loss, and immune dysfunction.

Abstract: The present invention provides a method of treating kidney or renal diseases/conditions in a subject by administering to the subject a pharmaceutically effective amount of a purified LAP peptide, a TSP-1 type 1 repeat peptide, or a fragment thereof to interfere with the activation process of TGF-&bgr; by thrombospondin-1 to reduce and/or prevent renal damage. The present invention further provides a method of improving renal function in a subject having impaired renal function by administering to the subject a pharmaceutically effective amount of a purified LAP peptide, a TSP-1 type 1 repeat peptide, or a fragment thereof.

Abstract: The invention provides a method of stimulating TGF-&bgr; activity, comprising contacting latent TGF-&bgr; with an amount of an activating peptide from TSP effective to convert latent TGF-&bgr; to active TGF-&bgr;. Also provided is a method of inhibiting the stimulation of TGF-&bgr; activity, comprising contacting latent TGF-&bgr; with an amount of an inhibiting peptide from TSP effective to inhibit conversion of latent of TGF-&bgr; to active TGF-&bgr;. The invention also provides a method of enhancing wound healing, comprising the step of administering to the wound site an amount of an activating peptide from TSP effective to convert latent TGF-&bgr; to active TGF-&bgr;, the activation of TGF-&bgr; resulting in enhanced wound healing.