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 CK2␣, the catalytic subunit of CK2, as a GNrelated, differentially expressed gene. Overexpression of CK2␣ 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 CK2␣ 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.antisense oligodeoxynucleotide ͉ microarray ͉ pharmacology G lomerulonephritis (GN) is a disease characterized by renal inflammation, causing destruction of glomeruli and adjacent structures, as well as loss of renal function. It is associated with conditions such as hematuria and proteinuria. Current treatment is still limited to supportive therapy, with or without nonspecific immunosuppressive drugs (1-3). Early cellular proliferation followed by subsequent fibrosis is a prominent hallmark of proliferative GN, and it may ultimately lead to end-stage renal disease (4). The involvement of extracellular stimuli, such as growth factors, cytokines, activated complement, and immune complexes in the pathogenesis of experimental and human GN has been known for many years. However, only recently have the intracellular mediators that transduce signals from noxious extracellular stimuli to unfettered cellular proliferation and accompanying excess extracellular matrix deposition begun to be unraveled (5). Experiments with cultured glomerular cells and certain animal models of experimental GN implicate the activation of extracellular signal-regulated kinase (ERK), which results in glomerular cellular proliferation (6).Protein kinase CK2 (formerly known as casein kinase II) is an extremely well conserved pleiotropic protein kinase with a growing list of Ͼ300 substrates, the majority of which are proteins implicated in signal transduction, gene expression, and transcription-related functions (7-11). Protein kinase CK2 is a ubiquitous heterotetrameric serine͞threonine protein kinase made up of two ␣ or ␣Ј catalytic subunits and two -regulatory subunits. CK2 is activated during cell division, cellular differentiation, and embryogenesis, an...
