Connective Tissue Growth Factor-2

Abstract

The present invention relates to a human CTGF-2 polypeptide and DNA (RNA) encoding such polypeptide. Also provided is a procedure for producing such polypeptide by recombinant techniques and antibodies and antagonist/inhibitors against such polypeptide. Also provided are methods of using the polypeptide therapeutically for enhancing the repair of connective and support tissue, promoting the attachment, fixation and stabilization of tissue implants and enhancing wound healing. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention are also disclosed.

1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the polypeptide comprising amino acid 1 to amino acid 381 as set forth in SEQ ID NO:2;    (b) a polynucleotide encoding the polypeptide comprising amino acid 25 to amino acid 381 as set forth in SEQ ID NO:2;    (c) a polynucleotide encoding the polypeptide comprising amino acids 1 to 351 of SEQ ID NO:2;    (d) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a) or (b); and    (e) a polynucleotide fragment of the polynucleotide of (a), (b), (c) or (d).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide which encodes a mature polypeptide having the amino acid sequence expressed by the DNA contained in ATCC Deposit No. 75804;    (b) a polynucleotide which encodes a polypeptide having the amino acid sequence expressed by the DNA contained in ATCC Deposit No. 75804;    (c) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a); and    (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c).    
     
     
         4 . The polynucleotide of  claim 1 , wherein said polynucleotide sequence comprising a polynucleotide sequence selected from the group consisting of: 
 (a) a polynucleotide sequence as set forth in SEQ ID No. 1 from nucleotide 1 to nucleotide 1146; and    (b) a polynucleotide sequence as set forth in SEQ ID No. 1 from nucleotide 73 to nucleotide 1146.    
     
     
         5 . A vector containing the DNA of  claim 2 .  
     
     
         6 . A host cell genetically engineered with the vector of  claim 5 .  
     
     
         7 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 6  and recovering the polypeptide encoded by said DNA.  
     
     
         8 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 5 .  
     
     
         9 . A polypeptide comprising a member selected from the group consisting of 
 (a) a mature polypeptide having the deduced amino acid sequence of SEQ ID NO:2 and fragments, analogs and derivatives thereof, and    (b) a mature polypeptide encoded by the cDNA of ATCC Deposit No. 75804 and fragments, analogs and derivatives of said polypeptide.    
     
     
         10 . The polypeptide of  claim 9  wherein the polypeptide comprises amino acid 25 to amino acid 381 of SEQ ID NO:2.  
     
     
         11 . An antibody that binds to the polypeptide of  claim 9 .  
     
     
         12 . A method of producing an antibody that binds the polypeptide of  claim 9  purified from a cell, said method comprising: 
 (a) introducing the polypeptide of  claim 9  into an animal;    (b) allowing the animal to generate an antibody that binds said polypeptide; and    (c) isolating the antibody from the animal.    
     
     
         10 . A compound which inhibits activation of the receptor for the polypeptide of  claim 9 .  
     
     
         14 . A compound which activates the receptor for the polypeptide of  claim 9 .  
     
     
         15 . A method for the treatment of a patient having need of CTGF-2 comprising: 
 administering to the patient a therapeutically effective amount of the polypeptide of  claim 9 .    
     
     
         16 . The method of  claim 15  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.  
     
     
         17 . A method for the treatment of a patient having need to inhibit a CTGF-2 polypeptide comprising: administering to the patient a therapeutically effective amount of the compound of claim  13 .  
     
     
         18 . A process for diagnosing a disease or a susceptibility to a disease related to an under-expression of the polypeptide of  claim 9  comprising: 
 determining a mutation in a nucleic acid sequence encoding said polypeptide.    
     
     
         19 . A diagnostic process comprising: 
 analyzing for the presence of the polypeptide of  claim 9  in a sample derived from a host.    
     
     
         20 . A method for identifying agonist or antagonist compounds to the polypeptide of  claim 9  comprising: 
 contacting a cell expressing on the surface thereof a receptor for the polypeptide, said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor, with an analytically detectable compound under conditions to permit binding to the receptor;    detecting the absence or presence of a signal generated from the interaction of the compound with the receptor.