Regulation of epithelial tissue by hedgehog-like polypeptides, and formulations and uses related thereto

Abstract

The present application is directed to the discovery that preparations of hedgehog polypeptides can be used to control the formation and/or maintenance of epithelial tissue.

1 . A method for inhibiting proliferation or differentiation of an internal epithelial cell or tissue in a post-natal mammal, comprising administering to a post-natal mammal in need thereof an amount of an agent effective to inhibit proliferation or differentiation of said epithelial cell or tissue in said mammal in need thereof, wherein the agent is a hedgehog antagonist or a patched agonist that inhibits hedgehog signal transduction. 
     
     
         2 . The method of  claim 1 , wherein the agent inhibits proliferation of epithelial cells in the tissue. 
     
     
         3 . The method of  claim 1 , wherein the internal epithelial cell or tissue is intestinal lining. 
     
     
         4 . The method of  claim 1 , wherein the internal epithelial cell or tissue are esophageal cells. 
     
     
         5 . The method of  claim 1 , wherein the post-natal mammal in need thereof is a post-natal mammal having a hyperplastic or neoplastic condition. 
     
     
         6 . The method of  claim 5 , wherein the hyperplastic or neoplastic condition is a carcinoma. 
     
     
         7 . A method for treating a hyperplastic or neoplastic condition in a post-natal mammal, comprising administering to a post-natal mammal in need thereof an effective amount of an agent, wherein the agent is a hedgehog antagonist or a patched agonist that inhibits hedgehog signal transduction, and wherein the agent inhibits proliferation or differentiation of internal epithelial cells or tissue. 
     
     
         8 . The method of  claim 7 , wherein the internal epithelial cells or tissue is intestinal lining. 
     
     
         9 . The method of  claim 7 , wherein the internal epithelial cells or tissue are esophageal cells. 
     
     
         10 . The method of  claim 7 , wherein said agent inhibits proliferation of internal epithelial cells. 
     
     
         11 . The method of  claim 7 , wherein the hyperplastic or neoplastic condition is a carcinoma. 
     
     
         12 . The method of  claim 7 , wherein the agent is administered as a therapeutic composition. 
     
     
         13 . A method for treating a hyperplastic or neoplastic condition of an internal epithelial tissue, comprising administering to a post-natal mammal in need thereof an effective amount of an agent, wherein the agent is a hedgehog antagonist or a patched agonist that inhibits hedgehog signal transduction. 
     
     
         14 . A method for increasing take rates of a skin graft in a post-natal mammal, comprising contacting said skin graft in said mammal with an effective amount of an agent, wherein said agent is a hedgehog agonist or patched antagonist that induces hedgehog signaling. 
     
     
         15 . A method for promoting the formation of gum tissue around natural or prosthetic teeth in a post-natal mammal, comprising administering to said mammal an effective amount of an agent, wherein the agent is a hedgehog agonist or a patched antagonist that induces hedgehog signaling.