Compositions and methods of using angiopoietin-like 4 protein

Abstract

ANGPTL4 compositions and methods of using such compositions, and agonists or antagonists thereof, for the diagnosis and treatment of diseases or disorders are included, including methods to modulate cell proliferation, cell adhesion, and cell migration.

1 . A method of stimulating proliferation of hepatocytes, the method comprising: 
 administering an effective amount of an angiopoietin-like 4 protein (ANGPTL4) to a population of hepatocytes or pre-hepatocytes thereby stimulating proliferation.    
     
     
         2 . The method of  claim 1 , wherein the hepatocytes are in a subject.  
     
     
         3 . The method of  claim 2 , wherein the subject is a human.  
     
     
         4 . The method of  claim 1 , wherein the ANGPTL4 comprises amino acid residues 23 to 406 of human ANGPTL4.  
     
     
         5 . The method of  claim 1 , wherein the ANGPTL4 comprises amino acid residues 184 to 406 of human ANGPTL4.  
     
     
         6 . The method of  claim 1 , wherein administration step comprises administering a nucleic acid sequence than encodes for the ANGPTL4.  
     
     
         7 . A method of stimulating proliferation of hepatocytes, the method comprising: administering an effective amount of an agent that stimulates production of an ANGPTL4 in hepatocytes or pre-hepatocytes, thereby stimulating proliferation.  
     
     
         8 . A method of inhibiting proliferation of hepatocytes, the method comprising administering an effective amount of an ANGPTL4 antagonist to a population of hepatocytes or pre-hepatocytes.  
     
     
         9 . The method of  claim 8 , wherein the antagonist is an agent that inhibits ANGPTL4 protein production in the hepatocyte.  
     
     
         10 . The method of  claim 8 , wherein the agent is an antisense or ribozyme molecule.  
     
     
         11 . The method of  claim 8 , wherein the ANGPTL4 antagonist is an anti-ANGPTL4 antibody.  
     
     
         12 . The method of  claim 8 , wherein the ANGPTL4 antagonist is an anti-αVβ5 antibody.  
     
     
         13 . A method of inducing cell adhesion of hepatocytes, the method comprising: 
 administering an effective amount of a composition comprising an ANGPTL4 to a population of hepatocytes, thereby inducing the cell adhesion of hepatocytes.    
     
     
         14 . The method of  claim 13 , wherein the ANGPTL4 comprises amino acid residues 23 to 406 of human ANGPTL4.  
     
     
         15 . The method of  claim 13 , wherein the ANGPTL4 comprises amino acids residues 185 to 406 of human ANGPTL4.  
     
     
         16 . The method of  claim 13 , wherein the composition comprises the ANGPTL4 with a carrier.  
     
     
         17 . A method of inhibiting cell adhesion of hepatocytes, the method comprising: 
 administering an effective amount of a composition comprising an ANGPTL4 antagonist to a population of hepatocytes, thereby inhibiting the cell adhesion of the hepatocytes.    
     
     
         18 . The method of  claim 17 , wherein the antagonist is an anti-ANGPTL4 antibody.  
     
     
         19 . The method of  claim 17 , wherine the antagonist is an anti-αVβ5 antibody.  
     
     
         20 . A method of stimulating proliferation of pre-adipocytes, the method comprising: 
 administering an effective amount of a composition comprising an ANGPTL4 or agonist to a population of preadipocytes, thereby inducing the proliferation of pre-adipocytes.    
     
     
         21 . The method of  claim 20 , wherein the preadipocytes are in a subject.  
     
     
         22 . The method of  claim 20 , wherein the subject is a human.  
     
     
         23 . The method of  claim 20 , wherein the composition comprises the ANGPTL4 with a carrier.  
     
     
         24 . The method of  claim 20 , wherein the ANGPTL4 comprises amino acid residues 23 to 406 of human ANGPTL4.  
     
     
         25 . The method of  claim 24 , wherein the ANGPTL4 comprises amino acid residues from about 23 to about 162.  
     
     
         26 . A method of inhibiting the proliferation of pre-adipocytes, the method comprising administering an effective amount of a composition comprising an ANGPTL4 antagonist to a population of preadipocytes.  
     
     
         27 . The method of  claim 26 , wherein the ANGPTL4 antagonist is an anti-ANGPTL4 antibody.  
     
     
         28 . A method of inhibiting a biological activity of ANGPTL4, the method comprising administering an ANGPTL4 antagonist that binds to C-terminal of ANGPTL4.  
     
     
         29 . The method of  claim 28 , wherein the ANGPTL4 antagonist is an anti-ANGPTL4 antibody.  
     
     
         30 . The method of  claim 28 , wherein the ANGPTL4 antagonist is an anti-αVβ5 antibody.  
     
     
         31 . The method of  claim 28 , wherein the ANGPTL4 antagonist blocks Angptl4 from binding to αVβ5.  
     
     
         32 . The method of  claim 28 , wherein the biological activity comprises inducing cell proliferation or cell differentiation.  
     
     
         33 . An antibody that binds to C-terminal of ANGPTL4.  
     
     
         34 . The antibody of  claim 32 , wherein the antibody is a neutralizing antibody.  
     
     
         35 . A composition comprising a variant of ANGPTL4, wherein the variant ANGPTL4 is not proleolytically processed.  
     
     
         36 . The composition of  claim 35 , wherein the variant of ANGPTL4 comprises an alteration of amino acid 162 and/or 164.  
     
     
         37 . The composition of  claim 36 , wherein the alteration is a substitution.  
     
     
         38 . The composition of  claim 37 , wherein the substitution is at position 162 and at position 164.