title: Inhibition of protein kinase CK2 prevents the progression of glomerulonephritis.
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.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 1111 Tebiro Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Masateru
authors.initials: M
authors.lastname: Yamada
authors.forename: Susumu
authors.initials: S
authors.lastname: Katsuma
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Adachi
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shiojima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okuno
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Koshimizu
authors.forename: Shigeo
authors.initials: S
authors.lastname: Fujii
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sekiya
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Tamura
authors.forename: Wako
authors.initials: W
authors.lastname: Yumura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nihei
authors.forename: Makio
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D047310:Apigenin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004642:Emodin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005921:Glomerulonephritis / Q000188:drug therapy*; D007106:Immune Sera / Q000008:administration & dosage; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000473:pathology; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020411:Oligonucleotide Array Sequence Analysis; D011239:Prednisolone; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms
chemical_list: D007106:Immune Sera; D020319:Oligodeoxyribonucleotides, Antisense; D021122:Protein Subunits; D047310:Apigenin; D011239:Prednisolone; D003404:Creatinine; D047390:Casein Kinase II; D004642:Emodin