Sugar chain-related gene and use thereof

Abstract

As a result of dedicated studies, the present inventors succeeded in discovering, for the first time, that fibrogenesis could be suppressed at the physiological tissue level by inhibiting sulfation at position 4 or 6 of GalNAc, which is a sugar that constitutes sugar chains. Furthermore, the present inventors conducted studies using various disease model animals, and as a result, successfully demonstrated that inhibitors of sulfation at position 4 or 6 of GalNAc had therapeutic effects on diseases caused by tissue fibrogenesis (tissue fibrogenic disorders).

1 : A tissue fibrogenesis suppressing-agent, comprising:
 an inhibitor of sulfation at position 4 or 6 of N-acetylgalactosamine,   wherein the inhibitor is an siRNA that suppresses expression of the GalNAc4S-6ST gene.   
     
     
         2 - 11 . (canceled) 
     
     
         12 : A method of producing a pharmaceutical composition comprising:
 (a) selecting, as a tissue fibrogenesis suppressing-agent, a compound that inhibits sulfation at position 4 or 6 of N-acetylgalactosamine that forms a sugar chain; and   (b) combining the compound with a pharmaceutically acceptable carrier.   
     
     
         13 : A method of treating a fibrogenic disorder, comprising:
 identifying a subject having a fibrogenic disorder of a tissue selected from the group consisting of cardiac tissue, gastrointestinal tissue, lung tissue, pancreatic tissue, kidney tissue, ocular tissue, cranial nerve tissue, and skin tissue; and   administering to the subject a therapeutically effective amount of an siRNA that suppresses expression of a gene encoding a sulfotransferase that transfers a sulfate to position 4 or 6 of N-acetylgalactosamine;   wherein the siRNA suppresses expression of a nucleotide sequence selected from the group consisting of a GalNAc4S-6ST gene, a GalNAc4ST-1 gene, a GalNAc4ST-2 gene, a C4ST-1 gene, a C4ST-2 gene, a C4ST-3 gene, a C6ST-1 gene, a C6ST-2 gene, and a D4ST gene.   
     
     
         14 : The method of  claim 13 , wherein the subject has a fibrogenic disorder of gastrointestinal tissues. 
     
     
         15 : The method of  claim 14 , wherein the siRNA suppresses expression of the GalNAc4S-6ST gene. 
     
     
         16 : The method of  claim 13 , wherein the gene encoding a sulfotransferase is a human gene. 
     
     
         17 : The tissue fibrogenesis suppressing-agent of  claim 1 , wherein the inhibitor is siRNA comprising the sequences of SEQ ID NO: 25 and SEQ ID NO: 26. 
     
     
         18 : The tissue fibrogenesis suppressing-agent of  claim 1 , comprising:
 the inhibitor; and   a pharmaceutically acceptable carrier.   
     
     
         19 : The tissue fibrogenesis suppressing-agent of  claim 17 , comprising:
 the inhibitor; and   a pharmaceutically acceptable carrier.   
     
     
         20 : A siRNA comprising the sequences of SEQ ID NO: 25 and SEQ ID NO: 26. 
     
     
         21 : A composition, comprising:
 the siRNA of  claim 20 ; and   a pharmaceutically acceptable carrier.   
     
     
         22 : A composition, comprising:
 the siRNA of  claim 20 ; and   a pharmaceutically acceptable carrier,   wherein the composition has a therapeutic effect on a tissue fibrogenic disorder.   
     
     
         23 : A composition, comprising:
 the siRNA of  claim 20 ; and   a pharmaceutically acceptable carrier,   wherein the composition has a therapeutic effect on an inflammatory bowel disease.   
     
     
         24 : A composition, comprising:
 the siRNA of  claim 20 ; and   a pharmaceutically acceptable carrier,   wherein the composition has a therapeutic effect on Crohn's disease.   
     
     
         25 : A composition, comprising:
 the siRNA of  claim 20 ; and   a pharmaceutically acceptable carrier,   wherein the composition has a therapeutic effect on ulcerative colitis.