Hyaluronic Acid Decomposition-Promoting Factor and Inhibitor Thereof

Abstract

The present invention is directed to KIAA1199, which is a novel factor involved in decomposition of hyaluronic acid, and to use thereof. More specifically, the invention is directed to a hyaluronic acid decomposition-promoting agent containing the KIAA1199 gene and a protein encoded by the gene; to a hyaluronic acid decomposition-inhibiting agent characterized by inhibiting the activity or expression thereof (including an siRNA or a monoclonal antibody); and to a method for screening a novel hyaluronic acid decomposition-controlling agent, in which the method contains employing the expression of KIAA1199 as an index.

What is claimed is:  
     
         1 .- 6 . (canceled) 
     
     
         7 . A method for controlling decomposition of hyaluronic acid, wherein the method comprises applying, to a subject in need thereof, the following i), ii) or iii), for improvement of joint functions, restoration of tissue, amelioration of skin roughness or dry skin, or reduction of wrinkles,
 i) an anti-sense nucleic acid or an siRNA against a KIAA1199 gene;   ii) an antibody specific to a protein encoded by the KIAA1199 gene; or   iii) a low-molecule compound selected from the group consisting of chlorpromazine, N-ethylmaleimide, bafilomycin A1, monensin, EDTA, deferoxamine, and orientin.   
     
     
         8 . A method for controlling decomposition of hyaluronic acid, wherein the method comprises applying to a subject in need thereof, the following i), ii) or iii): for tuning of tissue restoration by hyaluronic acid,
 i) a KIAA1199 gene;   ii) a protein encoded by the KIAA1199 gene; or   iii) a substance which can promote the expression or activity of the KIAA1199 gene or the protein encoded by the KIAA1199 gene.   
     
     
         9 .- 10 . (canceled) 
     
     
         11 . The method for controlling decomposition of hyaluronic acid according to  claim 7 , wherein the siRNA has a nucleotide sequence represented by any of SEQ ID NOs: 6 to 8 in the sequence list, or a nucleotide sequence having an identity of 90% or higher with respect thereto. 
     
     
         12 . The method for controlling decomposition of hyaluronic acid according to  claim 7 , wherein the antibody is specific to a peptide having an amino acid sequence represented by any of SEQ ID NOs: 3 to 5 in the sequence list, or an antibody which is specific to a peptide having an amino acid sequence having an identity of 90% or higher with respect thereto. 
     
     
         13 .- 18 . (canceled) 
     
     
         19 . A topical preparation comprising hyaluronic acid or a pharmacologically acceptable salt or a derivative thereof, and the following i), ii) or iii):
 i) an anti-sense nucleic acid or an siRNA against a KIAA1199 gene;   ii) an antibody specific to a protein encoded by the KIAA1199 gene; or   iii) a low-molecule compound selected from the group consisting of chlorpromazine, N-ethylmaleimide, bafilomycin A1, monensin, EDTA, deferoxamine, and orientin.   
     
     
         20 . The topical preparation according to  claim 19 , which is a joint function-improving agent or a tissue-restoring agent. 
     
     
         21 . The topical preparation according to  claim 19 , which is a cosmetic composition. 
     
     
         22 . A hyaluronic acid decomposition controlling effect assessing kit, comprising at least one of the following (a) to (d):
 (a) cells in which a KIAA1199 gene is highly expressed transiently or stably;   (b) a monoclonal antibody specific to a protein encoded by the KIAA1199 gene;   (c) an oligonucleotide primer for specifically amplifying the KIAA1199 gene; and   (d) a polynucleotide probe for detecting the KIAA1199 gene by binding specifically to the gene.   
     
     
         23 . The kit according to  claim 22 , wherein the monoclonal antibody is an antibody specific to a peptide having an amino acid sequence represented by any of SEQ ID NOs: 3 to 5 in the sequence list, or to a peptide having an amino acid sequence having an identity of 90% or higher with respect thereto. 
     
     
         24 . An anti-KIAA1199 monoclonal antibody which is specific to a peptide having an amino acid sequence represented by any of SEQ ID NOs: 3 to 5 in the sequence list, or to a peptide having an amino acid sequence having an identity of 90% or higher with respect thereto. 
     
     
         25 . A KIAA1199 epitope peptide having an amino acid sequence represented by any of SEQ ID NOs: 3 to 5 in the sequence list, or a KIAA1199 epitope peptide having an amino acid sequence having an identity of 90% or higher with respect thereto. 
     
     
         26 . The method for controlling decomposition of hyaluronic acid according to  claim 7 , which is applied for improvement of joint functions, or restoration of tissue. 
     
     
         27 . The method for controlling decomposition of hyaluronic acid according to  claim 7 , which is applied for amelioration of skin roughness or dry skin, or reduction of wrinkles. 
     
     
         28 . The topical preparation according to  claim 19 , wherein the siRNA has a nucleotide sequence represented by any of SEQ ID NOs: 6 to 8 in the sequence list, or a nucleotide sequence having an identity of 90% or higher with respect thereto. 
     
     
         29 . The topical preparation according to  claim 19 , wherein the antibody is specific to a peptide having an amino acid sequence represented by any of SEQ ID NOs: 3 to 5 in the sequence list, or an antibody which is specific to a peptide having an amino acid sequence having an identity of 90% or higher with respect thereto.