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Proc Natl Acad Sci U S A. 2005 May 24;102(21):7736-41. Epub 2005 May 16.

Inhibition of protein kinase CK2 prevents the progression of glomerulonephritis.

Author information

1
Pharmaceutical Research Laboratories, Toray Industries, Inc., 1111 Tebiro Kamakura, Kanagawa 248-8555, Japan.

Abstract

Glomerulonephritis (GN) is a progressive inflammation that may be caused by a variety of underlying disorders. It is the primary cause of chronic renal failure and end-stage renal disease, which require dialysis and transplantation worldwide. Immunosuppressive therapy has been used to treat GN clinically, but this treatment has had insufficient therapeutic effects. Here, we show that protein kinase CK2 is a key molecule in the progression of GN. cDNA microarray analysis identified CK2alpha, the catalytic subunit of CK2, as a GN-related, differentially expressed gene. Overexpression of CK2alpha was noted in the proliferative glomerular lesions in rat GN models and in renal biopsy specimens from lupus nephritis or IgA nephropathy patients. Administration of either antisense oligodeoxynucleotide against CK2alpha or low molecular weight CK2-specific inhibitors effectively prevented the progression of renal pathology in the rat GN models. The resolution of GN by CK2 inhibition may result from its suppression of extracellular signal-regulated kinase-mediated cell proliferation, and its suppression of inflammatory and fibrotic processes that are enhanced in GN. Our results show that CK2 plays a critical role in the progression of immunogenic renal injury, and therefore, CK2 is a potential target for GN therapy.

PMID:
15897466
PMCID:
PMC1140418
DOI:
10.1073/pnas.0409818102
[Indexed for MEDLINE]
Free PMC Article
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