Methods and compositions for stimulating and inhibiting...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 7/06 (2006.01) A61K 38/02 (2006.01) A61K 38/05 (2006.01) A61K 38/07 (2006.01) A61K 38/08 (2006.01) A61K 38/10 (2006.01) A61K 38/17 (2006.01) A61P 17/02 (2006.01) C07K 5/09 (2006.01) C07K 14/47 (2006.01) C07K 14/495 (2006.01)

Patent

CA 2590837

The invention provides a method of stimulating TGF-.beta. activity, comprising contacting latent TGF-.beta. with an amount of TSP or an activating peptide from TSP effective to convert latent TGF-.beta. to active TGF-.beta.. Also provided is a method of inhibiting the stimulation of TGF-.beta. activity, comprising contacting latent TGF-.beta. with a ligand specific for TSP effective to bind TSP and prevent activation of TGF-.beta. or an amount of an inhibiting peptide having a sequence that corresponds to a sequence of four consecutive amino acids of TSP, effective to inhibit the conversion of latent TGF-.beta. to active TGF-.beta.. The invention also provides a method of enhancing wound healing, comprising administering to a wound site an amount of TSP or an activating peptide from TSP effective to convert latent TGF-.beta. to active TGF-.beta., the activation of TGF-.beta. resulting in enhanced wound healing. A method of preventing fibrosis stimulated by TGF-.beta. in pathology is also provided. The method comprises administering to a site of potential fibrosis an amount of a ligand specific for TSP effective to bind TSP and inhibit activation of TGF-.beta. or an inhibiting peptide from TSP effective to inhibit conversion of latent TGF-.beta. to active TGF-.beta., resulting in reduced fibrosis. The invention also provides a method of blocking TGF-.beta.- mediated inhibition of endothelial cell proliferation comprising contacting endothelial cells with a ligand specific for TSP effective to bind TSP and inhibit activation of TGF- .beta. or an inhibiting peptide from TSP effective to inhibit conversion of latent TGF- .beta. to active TGF-.beta., resulting in proliferation of endothelial cells. The invention provides a method of stimulating TGF-.beta. activity, comprising contacting latent TGF-.beta. with an amount of TSP or an activating peptide from TSP effective to convert latent TGF-.beta. to active TGF-.beta.. Also provided is a method of inhibiting the stimulation of TGF-.beta. activity, comprising contacting latent TGF-.beta. with a ligand specific for TSP effective to bind TSP and prevent activation of TGF-.beta. or an amount of an inhibiting peptide having a sequence that corresponds to a sequence of four consecutive amino acids of TSP, effective to inhibit the conversion of latent TGF-.beta. to active TGF-.beta.. The invention also provides a method of enhancing wound healing, comprising administering to a wound site an amount of TSP or an activating peptide from TSP effective to convert latent TGF-.beta. to active TGF-.beta., the activation of TGF-.beta. resulting in enhanced wound bealing. A method of preventing fibrosis stimulated by TGF-.beta. in pathology is also provided. The method comprises administering to a site of potential fibrosis an amount of a ligand specific for TSP effective to bind TSP and inhibit activation of TGF-.beta. or an inhibiting peptide from TSP effective to inhibit conversion of latent TGF-.beta. to active TGF-.beta., resulting in reduced fibrosis. The invention also provides a method of blocking TGF-.beta.-mediated inhibition of endothelial cell proliferation comprising contacting endothelial cells with a ligand specific for TSP effective to bind TSP and inhibit activation of TGF-.beta. or an inhibiting peptide from TSP effective to inhibit conversion of latent TGF-.beta. to active TGF-.beta., resulting in proliferation of endothelial cells.

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