Therapeutic agents for renal diseases and method for screening the same

Abstract

The present invention provides a method for screening or identifying therapeutic or prophylactic agents for renal diseases, which comprises assaying a test substance for the activity of up-regulating the expression of fatty acid-binding protein (FABP), and novel mouse proximal renal tubular epithelial cell lines useful therein. The present invention also provides therapeutic or prophylactic agents for renal diseases comprising, as an active ingredient, an agent having activity of up-regulating FABP expression; agents for up-regulating the expression of FABP, and for treating or preventing renal diseases, which comprise a compound having activity of peroxisome proliferator-activated receptor (PPAR) agonist or carnitine palmitoyltransferase (CPT) inhibitor or the like.

1 . A therapeutic or prophylactic method for renal disease not caused by diabetes, which comprises administering to a patient in need thereof of an agent comprising, as an active ingredient, a compound having activity of peroxisome proliferator-activated receptor (PPAR) agonist.  
     
     
         2 . The therapeutic or prophylactic method of  claim 1 , wherein the renal disease is selected from the group consisting of glomerulonephritis, nephrotic syndrome, focal glomerulosclerosis, immune complex nephropathy, lupus nephritis, drug-induced renal injury and renal insufficiency.  
     
     
         3 . The therapeutic or prophylactic method of  claim 1 , wherein the renal disease is selected from the group consisting of nephrotic syndrome, focal glomerulosclerosis and drug-induced renal injury.  
     
     
         4 . The therapeutic or prophylactic method of  claim 1  wherein the compound having activity of PPAR agonist is MCC-555.  
     
     
         5 . A method for screening or identifying therapeutic or prophylactic agents for renal disease, which comprises the following steps of: 
 (A) assaying a test substance for the activity of up-regulating the expression of liver-type fatty acid-binding protein (L-FABP) in animal cell, wherein said assay comprises the step: 
 (1) culturing animal cell in the presence or absence of the test substance; and comparing the amount of L-FABP expressed in the cell in the presence of the test substance with the amount of L-FABP expressed in the cell in the absence of the test substance; or  
 (2) administering the test substance to an animal and comparing the amount of L-FABP expressed in renal tissues or cells of the animal with the amount of L-FABP expressed in renal tissues or cells of a non-treated animal; and  
   (B) selecting or identifying a substance having L-FABP up-regulating activity as a candidate therapeutic or prophylactic agent for renal diseases.