Premium
Protein kinase C β inhibition ameliorates experimental mesangial proliferative glomerulonephritis
Author(s) -
TOKUYAMA HIROBUMI,
KIM SANDRA,
ZHANG YUAN,
LANGHAM ROBYN G,
COX ALISON J.,
GOW RENAE M.,
KELLY DARREN J.,
GILBERT RICHARD E.
Publication year - 2011
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.2011.01475.x
Subject(s) - mesangial proliferative glomerulonephritis , protein kinase c , glomerulonephritis , medicine , diabetic nephropathy , mesangial cell , nephropathy , endocrinology , pathogenesis , extracellular matrix , cell growth , kinase , pharmacology , diabetes mellitus , kidney , biology , microbiology and biotechnology , biochemistry
Aim: 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. Conclusion: 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.