Inhibition of protein kinase CK2 prevents the progression of glomerulonephritis
Inhibition of protein kinase CK2 prevents the progression of glomerulonephritis
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DOI：
10.1073/pnas.0409818102
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发表时间：
2005-05-24
影响因子：
11.1
通讯作者：
Tsujimoto, G
中科院分区：
文献类型：
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作者：
Yamada, M;Katsuma, S;Tsujimoto, G
肾小球肾炎（GN）是一种进行性炎症，可能由多种基础疾病引起。它是慢性肾功能衰竭和终末期肾病的主要原因，在世界范围内需要透析和移植。免疫抑制疗法已被用于临床治疗GN，但这种治疗方法的治疗效果不够。在这里，我们表明，蛋白激酶CK2是一个关键分子在GN的进展。cDNA微阵列分析确定CK2 α，CK2的催化亚基，作为一个GN相关的，差异表达的基因。在大鼠GN模型的增生性肾小球病变和狼疮性肾炎或伊加肾病患者的肾活检标本中观察到CK 2 α过表达。在大鼠GN模型中，给予CK2 α或低分子量CK2特异性抑制剂的反义寡核苷酸可有效预防肾脏病理学的进展。通过CK2抑制来解决GN可能是由于其抑制细胞外信号调节激酶介导的细胞增殖，以及其抑制GN中增强的炎症和纤维化过程。我们的研究结果表明，CK2在免疫原性肾损伤的进展中起着至关重要的作用，因此，CK2是GN治疗的潜在靶点。
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 alpha, the catalytic subunit of CK2, as a GN-related, differentially expressed gene. Overexpression of CK2 alpha 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 alpha 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.