title: FK506 alleviates proteinuria in rats with adriamycin-induced nephropathy by down-regulating TRPC6 and CaN expression.
abstract: BACKGROUND
  To investigate the roles of transient receptor potential cation channel 6 (TRPC6) and calcineurin (CaN) in proteinuria pathogenesis and the mechanism of action of the calcineurin inhibitor tacrolimus (FK506) in adriamycin-induced nephropathy.
  
  
  METHODS
  The adriamycin-induced nephropathy rats were established and randomly divided into adriamycin nephropathy (ADR), low-dose FK506 treated (ADR + FK0.5), high-dose FK506 treated (ADR + FK1.0) and Control groups. Twenty-four hour urinary protein and blood biochemistry were measured on weeks 2, 3, 5 and 7, and the distributions and expressions of TRPC6 and CaN in the renal tissue were detected by immunohistochemistry, real-time PCR and Western blot.
  
  
  RESULTS
  The study showed the 24-hour urinary protein increased significantly in ADR rats compared with Controls whilst for ADR rats hypoalbuminemia, hypercholesterolemia, renal functional lesion and renal pathologic changes appeared. The areas and intensities of TRPC6 and CaN expressed in the glomerulus and tubulointerstitium of ADR rats increased significantly. The expression of TRPC6 mRNA in ADR rats began to increase on the 3rd week and persisted to the 7th week, and CaN mRNA increased throughout the period. Protein expressions of TRPC6 and CaN in ADR rats were significantly higher than those of Controls. FK506 can inhibit CaN activity in the renal tissues and further decrease TRPC6 expression and therefore reduce renal damage and proteinuria in a dose-dependent manner.
  
  
  CONCLUSIONS
  These findings suggested that TRPC6 and CaN were up-regulated on mRNA and protein levels in adriamycin-induced rats. FK506 had a therapeutic effect on the progression of proteinuria and renal damage by down-regulating of TRPC6 and CaN in the renal tissues.
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Liu
authors.forename: Zequan
authors.initials: Z
authors.lastname: Ji
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015153:Blotting, Western; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D065095:Calcineurin Inhibitors; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004317:Doxorubicin; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D011507:Proteinuria / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D004317:Doxorubicin; D019703:Calcineurin; D016559:Tacrolimus