Patent CA-2590837-A1 (CA)
Inventor: KRUTZSCH HENRY C
IPC: A61K47/56
Filed: 1994-08-12
Abstract: 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.