Stem cell factor-like proteins and uses thereof

Abstract

The invention relates to pharmaceutical compositions comprising gastrointestinal proliferative factor SCFA2, SCFA4 or SCFA4v polynucleotides and polypeptides. The invention further relates to the therapeutic use of SCFA2, SCFA4 or SCFA4v to prevent or treat conditions or disorders associated with the degeneration of the epithelial mucosa.

1 . An adenoviral vector comprising a gene encoding SEQ ID NO: 3, 6, 8, 10, 12, 14, 17, 19, 21, 23, 26, 36, 40, 44, 51, or 55 operably associated with an expression control sequence. 
     
     
         2 . A transgene construct comprising a nucleic acid encoding the polypeptide of SEQ ID NO: 23, 26, 44, fragment or analog thereof. 
     
     
         3 . An isolated polypeptide comprising an amino acid sequence which is at least 95% identical to the amino acid sequence of SEQ ID NOS. 26 or 44, or fragment or analog thereof. 
     
     
         4 . The polypeptide of  claim 3 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NOS: 26 or 44, or a fragment or analog thereof. 
     
     
         5 . A method for detecting a polynucleotide comprising the nucleotide sequence of SEQ ID NO:22 in a sample, comprising:
 (a) contacting the sample with a compound that binds to and forms a complex with said polynucleotide for a period sufficient to form the complex; and   (b) detecting the complex, so that if a complex is detected, said polynucleotide is detected.   
     
     
         6 . A method for detecting a polynucleotide comprising the nucleotide sequence of SEQ ID NO:22 in a sample, comprising:
 (a) contacting the same under stringent hybridization conditions with nucleic acid primers that anneal to said polynucleotide under such conditions;   (b) amplifying a product comprising at least a portion of said polynucleotide; and   (c) detecting said product and thereby said polynucleotide in the sample.   
     
     
         7 . The method of  claim 6 , wherein the polynucleotide is an RNA molecule and the method further comprises reverse transcribing an annealed RNA molecule into a cDNA polynucleotide. 
     
     
         8 . A method for detecting the polypeptide of  claim 3  in a sample, comprising:
 (a) contacting the sample with a compound that binds to and forms a complex with a polypeptide under conditions and for a period sufficient to form the complex; and   (b) detecting formation of the complex, so that if a complex formation is detected, the polypeptide of  claim 3  is detected.   
     
     
         9 . A method for identifying a compound that binds to the polypeptide of  claim 3 , comprising:
 (a) contacting the compound with the polypeptide of  claim 3  under conditions sufficient to form a polypeptide/compound complex; and   (b) detecting the complex, so that if the polypeptide/compound complex is detected, a compound that binds to the polypeptide of  claim 3  is identified.   
     
     
         10 . A method for identifying a compound that binds to the polypeptide of  claim 3 , comprising:
 (a) contacting the compound with the polypeptide  claim 3 , in a cell, under conditions sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a reporter gene sequence in the cell; and   (b) detecting the complex by detecting reporter gene sequence expression, so that if the polypeptide/compound complex is detected, a compound that binds to the polypeptide of  claim 3  is identified.   
     
     
         11 . A composition comprising a therapeutically effective amount of a polypeptide of SEQ ID NO: 3, 6, 8, 10, 12, 14, 17, 19, 21, 23, 26, 36, 40, 44, 51, or 55, fragment, or analog thereof, and a pharmaceutically acceptable carrier. 
     
     
         12 . A method of stimulating epithelial cell proliferation in a subject comprising administering to a mammalian subject in need thereof a therapeutically effective amount of the composition of  claim 11 . 
     
     
         13 . The method of  claim 12 , wherein the subject has mucositis, inflammatory bowel disease, or short bowel syndrome. 
     
     
         14 . The method of  claim 12 , wherein the mammalian subject is a human.