Methods for promoting wound healing and/or reducing scar formation

Abstract

The present invention provides methods for promoting wound healing and/or reducing scar formation, by administering to an individual in need thereof one or more of the heat shock protein 20-derived polypeptides disclosed herein.

We claim: 
     
         1 . A method for reducing scar formation, comprising administering to an individual in need thereof an amount effective to reduce scar formation of a polypeptide comprising a sequence according general formula I:
   X1-A(X2)APLP-X3   wherein X1 is 0-14 amino acids of the sequence of heat shock protein 20 between residues 1 and 14 of SEQ ID NO: 298;   X2 is selected from the group consisting of S, T, Y, D, B, hydroxylysine, hydroxyproline, phosphoserine analogs and phosphotyrosine analogs; and   X3 is selected from the group consisting of (a) 0-140 amino acids of heat shock protein 20 between residues 21 and 160 of SEQ ID NO:298; and (b) 0, 1, 2, or 3 amino acids of a sequence of genus Z1-Z2-Z3, wherein Z1 is selected from the group consisting of G and D;   Z2 is selected from the group consisting of L and K; and   Z3 is selected from the group consisting of S, T, and K.   
     
     
         2 . The method of  claim 1  wherein X1 is 0-14 amino acids of the sequence of heat shock protein 20 between residues 1 and 14 of SEQ ID NO: 298. 
     
     
         3 . The method of  claim 1  wherein the polypeptide comprises an amino acid sequence of SEQ ID NO:298. 
     
     
         4 . The method of  claim 1  wherein X2 is selected from the group consisting of S, T, and Y, and wherein X2 is phosphorylated. 
     
     
         5 . The method of  claim 4  wherein X2 is S. 
     
     
         6 . The method of  claim 1  wherein the polypeptide comprises a sequence according to SEQ ID NO:300. 
     
     
         7 . The method of  claim 1  wherein the polypeptide comprises a polypeptide of the formula:
   B1-X1-A(X2)APLP-X3-B2 
 wherein X1, X2, and X3 are as defined above, and wherein B1 and B2 are independently absent or comprise a transduction domain, as described above. 
 
     
     
         8 . The method of  claim 7  wherein one or both of B1 and B2 comprises the amino acid sequence of SEQ ID NO:299 and/or SEQ ID NO:281. 
     
     
         9 . The method of  claim 1  wherein the polypeptide comprises a polypeptide of SEQ ID NO:301 or SEQ ID NO:315. 
     
     
         10 . The method of  claim 1  wherein the polypeptide comprises a polypeptide of the formula:
   J1-J2-X1-A(X2)APLP-X3-J3 
 wherein X1, X2, and X3 are as defined above, wherein J2 and J3 are independently absent or comprise a transduction domain, and wherein J1 is absent or is one or more molecules comprising one or more aromatic ring. 
 
     
     
         11 . The method of  claim 1  wherein the individual in need thereof has a wound selected from the group consisting of lacerations; burns; punctures; pressure sores; bed sores; canker sores; trauma, bites; fistulas; ulcers; lesions caused by infections; periodontal wounds; endodontic wounds; burning mouth syndrome; laparotomy wounds; surgical wounds; incisional wounds; contractures after burns; tissue fibrosis; and wounds resulting from cosmetic surgical procedures 
     
     
         12 . The method of  claim 1  wherein the method is used for reducing initial scar formation. 
     
     
         13 . A method for promoting wound healing, comprising administering to an individual in need thereof an amount effective to promote wound healing of a polypeptide comprising a sequence according general formula I:
   X1-A(X2)APLP-X3   wherein X1 is 0-14 amino acids of the sequence of heat shock protein 20 between residues 1 and 14 of SEQ ID NO: 298;   X2 is selected from the group consisting of S, T, Y, D, B, hydroxylysine, hydroxyproline, phosphoserine analogs and phosphotyrosine analogs; and   X3 is selected from the group consisting of (a) 0-140 amino acids of heat shock protein 20 between residues 21 and 160 of SEQ ID NO:298; and (b) 0, 1, 2, or 3 amino acids of a sequence of genus Z1-Z2-Z3, wherein Z1 is selected from the group consisting of G and D;   Z2 is selected from the group consisting of L and K; and   Z3 is selected from the group consisting of S, T, and K.   
     
     
         14 . The method of  claim 13  wherein X1 is 0-14 amino acids of the sequence of heat shock protein 20 between residues 1 and 14 of SEQ ID NO: 298. 
     
     
         15 . The method of  claim 13  wherein the polypeptide comprises an amino acid sequence of SEQ ID NO:298. 
     
     
         16 . The method of  claim 13  wherein X2 is selected from the group consisting of S, T, and Y, and wherein X2 is phosphorylated. 
     
     
         17 . The method of  claim 16  wherein X2 is S. 
     
     
         18 . The method of  claim 13  wherein the polypeptide comprises a sequence according to SEQ ID NO:300. 
     
     
         19 . The method of  claim 13  wherein the polypeptide comprises a polypeptide of the formula:
   B1-X1-A(X2)APLP-X3-B2 
 wherein X1, X2, and X3 are as defined above, and wherein B1 and B2 are independently absent or comprise a transduction domain, as described above. 
 
     
     
         20 . The method of  claim 19  wherein one or both of B1 and B2 comprises the amino acid sequence of SEQ ID NO:299 and/or SEQ ID NO:281. 
     
     
         21 . The method of  claim 13  wherein the polypeptide comprises a polypeptide of SEQ ID NO:301 or SEQ ID NO:315. 
     
     
         22 . The method of  claim 13  wherein the polypeptide comprises a polypeptide of the formula:
   J1-J2-X1-A(X2)APLP-X3-J3 
 wherein X1, X2, and X3 are as defined above, wherein J2 and J3 are independently absent or comprise a transduction domain, and wherein J1 is absent or is one or more molecules comprising one or more aromatic ring. 
 
     
     
         23 . The method of  claim 13  wherein the individual in need thereof has a wound selected from the group consisting of lacerations; burns; punctures; pressure sores; bed sores; canker sores; trauma, bites; fistulas; ulcers; lesions caused by infections; periodontal wounds; endodontic wounds; burning mouth syndrome; laparotomy wounds; surgical wounds; incisional wounds; contractures after burns; tissue fibrosis; and wounds resulting from cosmetic surgical procedures