Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis
Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis
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DOI：
10.1152/ajprenal.00374.2010
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发表时间：
2010-12-01
影响因子：
4.2
通讯作者：
Kumagai, Hiroo
中科院分区：
文献类型：
--
作者：
Hyodo, Toshitake;Oda, Takashi;Kumagai, Hiroo
Hyodo T，Oda T，菊池Y，Higashi K，Kushiyama T，Yamamoto K，Yamada M，Suzuki S，Hokari R，Kinoshita M，Seki S，Fujinaka H，Yamamoto T，Miura S，Kumagai H.电压门控性钾通道Kv1.3阻断剂对大鼠抗肾小球基底膜肾炎的潜在治疗作用美国肾脏生理学杂志299：F1258-F1269，2010年。首次发表于2010年9月1日; doi：10.1152/ajprenal.00374.2010.-电压门控钾通道Kv1.3最近被确定为允许效应记忆T细胞（T-EM）的选择性药理学抑制而不影响原始T细胞（T-N）和中央记忆T细胞（T-CM）的功能的分子靶标。我们发现Kv1.3在抗肾小球基底膜肾炎（anti-GBM GN）大鼠的肾小球和部分肾小管上表达。使用肾细胞的流式细胞术分析显示，大多数CD 4（+）T细胞和一些CD 8（+）T细胞具有T-EM表型（CD 45 RC（-）CD 62 L（-））。使用从抗GBM GN肾脏分离的单核细胞悬液进行双重免疫荧光染色显示，Kv1.3在T细胞和一些巨噬细胞上表达。因此，我们研究了Kv1.3阻断剂Psora-4是否可用于治疗抗GBM GN。对注射了兔抗大鼠GBM抗体的大鼠也进行Psora-4或溶媒的腹腔内注射。给予Psora-4的大鼠比给予载体的大鼠表现出更少的蛋白尿和更少的新月体肾小球。这些结果表明，T-EM和一些表达Kv1.3通道的巨噬细胞在新月体GN的发病机制中起着关键作用，Psora-4将用于治疗快速进展性肾小球肾炎。
Hyodo T, Oda T, Kikuchi Y, Higashi K, Kushiyama T, Yamamoto K, Yamada M, Suzuki S, Hokari R, Kinoshita M, Seki S, Fujinaka H, Yamamoto T, Miura S, Kumagai H. Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis. Am J Physiol Renal Physiol 299: F1258-F1269, 2010. First published September 1, 2010; doi:10.1152/ajprenal.00374.2010.-The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (T-EM) without affecting the function of nave T cells (T-N) and central memory T cells (T-CM). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4(+) T cells and some of the CD8(+) T cells had the T-EM phenotype (CD45RC(-)CD62L(-)). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kv1.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kv1.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been given an injection of rabbit anti-rat GBM antibody were also injected with Psora-4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria and fewer crescentic glomeruli than rats given the vehicle. These results suggest that T-EM and some macrophages expressing Kv1.3 channels play a critical role in the pathogenesis of crescentic GN and that Psora-4 will be useful for the treatment of rapidly progressive glomerulonephritis.