Connective tissue growth factor fragments and methods and uses thereof

Abstract

The present invention is directed to CTGF fragments comprising at least exon 4 or exon 5 of CTGF and having mitogenic activity. The present invention is further directed to methods using said CTGF fragments to identify compositions which modulate the mitogenic activity of said CTGF fragments and to the compositions so identified.

We claim:  
     
         1 . A fragment of connective tissue growth factor (CTGF) polypeptide having mitogenic activity.  
     
     
         2 . The fragment of  claim 1 , comprising an amino acid sequence encoded by at least exon 4 as set forth in FIG. 2.  
     
     
         3 . The fragment of  claim 1 , comprising an amino acid sequence encoded by at least exon 5 as set forth in FIG. 2.  
     
     
         4 . The fragment of  claim 1 , comprising an amino acid sequence encoded by at least exons 4 and 5 as set forth in FIG. 2.  
     
     
         5 . A polynucleotide encoding a fragment as in  claim 1 .  
     
     
         6 . An antibody that specifically binds to a CTGF fragment of  claim 1 .  
     
     
         7 . An antisense molecule that binds to a nucleic acid sequence encoding a CTGF fragment of  claim 1 .  
     
     
         8 . A method for treating a CTGF-associated disease or disorder comprising administering to a subject having or at risk of having a CTGF-associated disease or disorder, an antibody of  claim 6 .  
     
     
         9 . The method of  claim 8 , wherein the disease or disorder is a fibroproliferative disease/disorder.  
     
     
         10 . The method of  claim 8 , wherein the disease or disorder is selected from the group consisting of kidney fibrosis, scleroderma, pulmonary fibrosis, liver fibrosis, arthritis, hypertropic scarring, atherosclerosis, diabetic nephropathy and retinopathy, hypertension, kidney disorders, angiogenesis-related disorders, skin fibrotic disorders, and cardiovascular disorders.  
     
     
         11 . A method for treating a CTGF-associated disease or disorder comprising administering to a subject having or at risk of having a CTGF-associated disease or disorder, an antisense molecule of  claim 7 .  
     
     
         12 . A method of identifying an agent or compound that modulates mitogenic activity of a CTGF fragment comprising: 
 contacting a cell with a test agent and with a mitogenic CTGF fragment under conditions that allow the components to interact; and    comparing the ability of the cell to proliferate in the presence of the agent to the ability of a cell to proliferate in the absence of the agent, wherein a difference in the proliferative ability of the cells is indicative of an agent or compound that modulates mitogenic activity of a CTGF fragment.    
     
     
         13 . The method of  claim 12 , wherein the modulation is inhibition of activity.  
     
     
         14 . The method of  claim 12 , wherein the modulation is stimulation of activity.