Identification of novel anti-fibrotic peptide in c-terminal region of the met receptor tyrosine kinase

Abstract

The invention provides anti-fibrotic peptides derived from the C-terminal region of the MET receptor tyrosine kinase. Polynucleotides encoding these peptides, host cells transformed with the polynucleotides, and methods of using these peptides and polynucleotides are included in the invention. Uses of these peptides, polynucleotides and expression vectors include the treatment of fibrosis in a subject.

1 - 22 . (canceled) 
     
     
         23 . A method of inhibiting apoptosis in a cell, the method comprising contacting a cell with an effective amount of a composition comprising an isolated C-terminal peptide of the MET receptor, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 4 and a variant thereof, thereby inhibiting apoptosis in the cell. 
     
     
         24 . The method of  claim 23 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and a variant thereof. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 23 , wherein the peptide comprises a caspase-3 cleavage site. 
     
     
         27 . The method of  claim 23 , wherein the N-terminus of the peptide is acetylated. 
     
     
         28 . The method of  claim 23 , wherein the composition comprises a pharmaceutical composition comprising the peptide and a pharmaceutically acceptable carrier. 
     
     
         29 . A method of inhibiting apoptosis in a cell, the method comprising contacting a cell with an effective amount of a composition comprising an isolated polynucleotide encoding a C-terminal peptide of the MET receptor, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 4 and a variant thereof, thereby inhibiting apoptosis in the cell. 
     
     
         30 . The method of  claim 29 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and a variant thereof. 
     
     
         31 . The method of  claim 29 , wherein the peptide comprises a caspase-3 cleavage site. 
     
     
         32 . The method of  claim 29 , wherein the polynucleotide is operably linked to a promoter. 
     
     
         33 . The method of  claim 29 , wherein the composition comprises an expression vector comprising the isolated polynucleotide. 
     
     
         34 . The method of  claim 29 , wherein the composition comprises a pharmaceutical composition comprising the polynucleotide and a pharmaceutically acceptable carrier.