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钾通道敲低对新疆哈萨克族高血压患者外周血T淋巴细胞及NFAT信号通路的影响

Effects of potassium channel knockdown on peripheral blood T lymphocytes and NFAT signaling pathway in Xinjiang Kazak patients with hypertension.

作者信息

Dai Chen, Tan Meng, Meng Xiaopan, Dong Jian, Zhang Yuanming

机构信息

Department of Nephrology, Renal Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.

Heart Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.

出版信息

Clin Exp Hypertens. 2023 Dec 31;45(1):2169449. doi: 10.1080/10641963.2023.2169449.

Abstract

BACKGROUD AND AIM

T lymphocytes are involved in the occurrence and development of essential hypertension, and potassium channels are thought to be critical for lymphocyte activation. This study is to examine the roles of the voltage-gated potassium channels (Kv1.3) and calcium-activated potassium channels (KCa3.1) in peripheral blood T lymphocytes in Kazakh hypertensive patients of Xinjiang, China, mainly focusing on the effects of these channels on nuclear factor of activated T cells (NFAT) and inflammatory cytokines of T lymphocytes.

METHOD

Kv1.3 and KCa3.1 gene silencing were performed in cultured T lymphocytes from Kazakh patients with severe hypertension. T cell proliferation after gene silencing was measured using CCK-8. The mRNA and protein expression levels were measured using RT-qPCR and Western blot analysis, respectively. Nuclear translocation of NFAT was observed using laser confocal fluorescence microscopy. Inflammatory cytokine levels were detected with ELISA.

RESULTS

Compared with control group, gene silencing of Kv1.3 and KCa3.1 respectively inhibited the proliferation of T cells. Moreover, compared with the control group, the mRNA expression levels of and were significantly decreased after gene silencing. Furthermore, the NFAT protein expression level was significantly down-regulated. In addition, the levels of IFN-γ and IL-6 in the cell culture supernatant were significantly decreased.

CONCLUSION

Both Kv1.3 and KCa3.1 potassium channels activated T lymphocytes and enhanced the cytokine secretion possibly through CaN/NFAT signaling pathway, which may in turn induce micro-inflammatory responses and trigger the occurrence and progression of hypertension.

摘要

背景与目的

T淋巴细胞参与原发性高血压的发生发展,钾通道被认为对淋巴细胞激活至关重要。本研究旨在探讨电压门控钾通道(Kv1.3)和钙激活钾通道(KCa3.1)在中国新疆哈萨克族高血压患者外周血T淋巴细胞中的作用,主要关注这些通道对活化T细胞核因子(NFAT)和T淋巴细胞炎性细胞因子的影响。

方法

对重度高血压哈萨克族患者培养的T淋巴细胞进行Kv1.3和KCa3.1基因沉默。使用CCK-8检测基因沉默后T细胞的增殖情况。分别使用RT-qPCR和蛋白质免疫印迹分析检测mRNA和蛋白质表达水平。使用激光共聚焦荧光显微镜观察NFAT的核转位。用ELISA检测炎性细胞因子水平。

结果

与对照组相比,Kv1.3和KCa3.1基因沉默分别抑制了T细胞的增殖。此外,与对照组相比,基因沉默后 和 的mRNA表达水平显著降低。此外,NFAT蛋白表达水平显著下调。此外,细胞培养上清液中IFN-γ和IL-6水平显著降低。

结论

Kv1.3和KCa

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