Inhibition of Protein Kinase CK2 Prevents the Progression of Glomerulonephritis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 May 18

PMID 15897466

Citations 30

Authors

Masateru Yamada

Susumu Katsuma

Tetsuya Adachi

Akira Hirasawa

Satoshi Shiojima

Tadashi Kadowaki

Yasushi Okuno

Taka-aki Koshimizu

Shigeo Fujii

Yumiko Sekiya

Yohei Miyamoto

Mitsutaka Tamura

Wako Yumura

Hiroshi Nihei

Makio Kobayashi

Gozoh Tsujimoto

Affiliations

Soon will be listed here.

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.

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