Inhibitors of cell regulatory factors and methods for preventing or reducing scarring

Abstract

The present invention provides a method of inhibiting an activity of a cell regulatory factor comprising contacting the cell regulatory factor with a purified polypeptide, wherein the polypeptide comprises the cell regulatory factor binding domain of a protein and wherein the protein is characterized by a leucine-rich repeat of about 24 amino acids. In a specific embodiment, the present invention relates to the ability of decorin, a 40,000 dalton protein that usually carries a glycosaminoglycan chain, to bind TGF-β. The invention also provides a novel cell regulatory factor designated MRF. Also provided are methods of identifying, detecting and purifying cell regulatory factors and proteins which bind and affect the activity of cell regulatory factors. The present invention further relates to methods for the prevention or reduction of scarring by administering decorin or a functional equivalent of decorin to a wound. The methods are particularly useful for dermal wounds resulting from burns, injuries or surgery. In addition, the present invention includes pharmaceutical compositions containing decorin or its functional equivalent and a pharmaceutically acceptable carrier useful in such methods. Finally, methods for preventing or inhibiting pathological conditions by administering decorin are also provided.

We claim:  
     
         1 . A method for the prevention or reduction of scarring comprising administering decorin or a functional equivalent of decorin to a wound.  
     
     
         2 . The method of  claim 1 , wherein said functional equivalent is biglycan.  
     
     
         3 . The method of  claim 1 , wherein said functional equivalent is fibromodulin.  
     
     
         4 . The method of  claim 1 , wherein said scarring is dermal scarring.  
     
     
         5 . A pharmaceutical composition comprising decorin or its functional equivalent and a pharmaceutically acceptable carrier.  
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein said functional equivalent is biglycan.  
     
     
         7 . The pharmaceutical composition of  claim 5 , wherein said functional equivalent is fibromodulin.  
     
     
         8 . The pharmaceutical composition of  claim 5 , wherein said pharmaceutically acceptable carrier is hyaluronic acid.  
     
     
         9 . The pharmaceutical composition of  claim 5 , wherein said composition further comprises an RGD-containing polypeptide attached to a biodegradable polymer.  
     
     
         10 . A method of treating a pathology caused by a TGF-β regulated activity comprising contacting the TGF-β with a purified polypeptide, wherein the polypeptide comprises a TGF-β binding domain of a protein and wherein the protein is characterized by a leucine-rich repeat of about 24 amino acids, whereby the pathology causing activity is prevented or reduced.  
     
     
         11 . The method of  claim 10 , wherein said protein is decorin.  
     
     
         12 . The method of  claim 10 , wherein said protein is biglycan.  
     
     
         13 . The method of  claim 10 , wherein said protein is fibromodulin.  
     
     
         14 . The method of  claim 10 , wherein said pathology is rheumatoid arthritis, glomerulonephritis, arteriosclerosis, adult respiratory distress syndrome, cirrhosis of the liver, fibrotic cancer, fibrosis of the lungs, post-myocardial infarction, cardiac fibrosis, post-angioplasty restenosis, renal interstitial fibrosis or dermal fibrotic conditions.  
     
     
         15 . The method of  claim 14 , wherein said pathology is glomerulonephritis.