Compositions and methods for improving kidney function

Abstract

Materials and methods for improving kidney function or enhancing proliferation or survival of kidney tubule epithelial cells or epithelial cell precursors in a mammal are disclosed. The methods comprise administering to the mammal a composition comprising a therapeutically effective amount of a zvegf4 protein or a zvegf4 protein-encoding polynucleotide in combination with a pharmaceutically acceptable delivery vehicle. Zvegf4 proteins include, for example, disulfide-bonded dimers of two polypeptide chains, each comprising residues 258-370 of SEQ ID NO:2.

1 . A method of improving kidney function in a mammal in need thereof, comprising administering to the mammal a composition comprising a therapeutically effective amount of a zvegf4 protein or zvegf4 protein-encoding polynucleotide, in combination with a pharmaceutically acceptable delivery vehicle, wherein the zvegf4 protein is a disulfide-bonded dimer of two polypeptide chains, each of said chains consisting of residues x-y of SEQ ID NO:2, inclusive, wherein the protein is optionally glycosylated, and wherein: 
 x is selected from the group consisting of 16, 17, 18, 19, 20, 21, 22, 24, 25, 35, 52, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 246, 250, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, and 263; and    y is selected from the group consisting of 365, 366, 367, 368, 369, and 370.    
     
     
         2 . The method of  claim 1  wherein x is selected from the group consisting of 19, 24, 25, 35, 52, 180, 246, 250, and 258.  
     
     
         3 . The method of  claim 1  wherein x is 258±5.  
     
     
         4 . The method of  claim 1  wherein y is 370.  
     
     
         5 . The method of  claim 1  wherein x is 258 and y is 370.  
     
     
         6 . The method of  claim 1  wherein x is 250 and y is 370.  
     
     
         7 . The method of  claim 1  wherein x is 246 and y is 370.  
     
     
         8 . The method of  claim 1  wherein a zvegf4 protein is administered to the mammal.  
     
     
         9 . The method of  claim 1  wherein a zvegf4 protein-encoding polynucleotide is administered to the mammal.  
     
     
         10 . The method of  claim 9  wherein said polynucleotide comprises an operably linked transcription promoter.  
     
     
         11 . The method of  claim 9  wherein said polynucleotide is a viral vector or plasmid.  
     
     
         12 . The method of  claim 1  wherein the mammal is suffering from acute tubular necrosis.  
     
     
         13 . A method of enhancing proliferation or survival of kidney tubule epithelial cells or epithelial cell precursors in a mammal, comprising administering to the mammal a composition comprising a therapeutically effective amount of a zvegf4 protein-encoding polynucleotide, in combination with a pharmaceutically acceptable delivery vehicle, wherein the zvegf4 protein is a disulfide-bonded dimer of two polypeptide chains, each of said chains consisting of residues x-y of SEQ ID NO:2, inclusive, wherein the protein is optionally glycosylated, and wherein: 
 x is selected from the group consisting of 16, 17, 18, 19, 20, 21, 22, 24, 25, 35, 52, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 246, 250, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, and 263; and    y is selected from the group consisting of 365, 366, 367, 368, 369, and 370.    
     
     
         14 . The method of  claim 13  wherein x is selected from the group consisting of 19, 24, 25, 35, 52, 180, 246, 250, and 258.  
     
     
         15 . The method of  claim 13  wherein x is 258±5.  
     
     
         16 . The method of  claim 13  wherein y is 370.  
     
     
         17 . The method of  claim 13  wherein x is selected from the group consisting of 258, 250, and 246; and wherein y is 370.  
     
     
         18 . The method of  claim 13  wherein said polynucleotide comprises an operably linked transcription promoter.  
     
     
         19 . The method of  claim 13  wherein said polynucleotide is a viral vector or plasmid.