title: Protein kinase C β inhibition ameliorates experimental mesangial proliferative glomerulonephritis.
abstract: OBJECTIVE
  Activation of protein kinase C (PKC) has been implicated in the pathogenesis of diabetic nephropathy where therapy targeting the β isoform of this enzyme has been examined. However, PKC-β is also increased in various forms of human glomerulonephritis, including IgA nephropathy. Accordingly, we sought to examine the effects of PKC-β inhibition in the Thy1.1 model of mesangial proliferative glomerulonephritis.
  
  
  METHODS
  Following administration of monoclonal OX-7, anti-rat Thy-1.1 antibody, Male Wistar rats were randomized to receive either the PKC-β inhibitor, ruboxistaurin (10 mg/kg per day in chow) or vehicle. Animals were then examined 6 days later.
  
  
  RESULTS
  PKC-β inhibition was associated with reductions in mesangial cellularity and extracellular matrix deposition. Proteinuria was, however, unaffected. In vitro, PKC-β inhibition showed modest, dose-dependent reductions in mesangial cell (3) H-thymidine and (3) H-proline incorporations, indices of cell proliferation and collagen synthesis, respectively.
  
  
  CONCLUSIONS
  The amelioration of the pathological findings of experimental mesangial proliferative glomerulonephritis by PKC-β inhibition suggests the potential clinical utility of this approach as a therapeutic strategy in non-diabetic glomerular disease.
authors.affiliation: Department of Medicine, University of Melbourne, St. Vincent's Hospital, Melbourne, Victoria, Australia.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tokuyama
authors.forename: Sandra
authors.initials: S
authors.lastname: Kim
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Robyn G
authors.initials: RG
authors.lastname: Langham
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Cox
authors.forename: Renae M
authors.initials: RM
authors.lastname: Gow
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007211:Indoles; D008301:Maleimides; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D018800:Thy-1 Antigens; C099154:ruboxistaurin; D003094:Collagen; D011493:Protein Kinase C; D064546:Protein Kinase C beta