HIPK3 Mediates Inflammatory Cytokines and Oxidative Stress Markers in Monocytes in a Rat Model of Sepsis Through the JNK/c-Jun Signaling Pathway
HIPK3 Mediates Inflammatory Cytokines and Oxidative Stress Markers in Monocytes in a Rat Model of Sepsis Through the JNK/c-Jun Signaling Pathway
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DOI：
10.1007/s10753-020-01200-5
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发表时间：
2020-04-30
期刊：
影响因子：
5.1
通讯作者：
Han, Xuehua
中科院分区：
文献类型：
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作者：
Liu, Ben;Hou, Qiuyue;Han, Xuehua
败血症是一种胎儿免疫功能紊乱，血液透析患者易发生败血症并发症，增加死亡风险。本研究旨在探讨同源域相互作用蛋白激酶3（homeodomain-interacting protein kinase 3，HIPK3）通过调控c-Jun氨基末端激酶（c-Jun amino-terminal kinase，JNK）/c-Jun信号通路对脓毒症大鼠单核细胞炎症因子和氧化应激标志物的影响。脓毒症的大鼠模型最初使用盲肠结扎和穿孔（CLP）建立，并通过扩大的脾组织、炎症和氧化应激进一步鉴定。从患有CLP诱导的脓毒症的大鼠中分离单核细胞。在CLP诱导的脓毒症大鼠单核细胞中，观察到HIPK3下调，而JUN上调。此外，用表达HIPK3或针对HIPK3的shRNA的慢病毒载体转导分离的单核细胞，以探索HIPK3对单核细胞活力和凋亡以及炎症因子和氧化应激标志物的影响。所获得的数据表明，HIPK3的过表达或JNK信号通路的抑制增强了单核细胞的增殖，减少了单核细胞的凋亡，减轻了炎症和氧化应激损伤。因此，我们的研究结果可能提供证据表明，HIPK3可以抑制JNK/c-Jun信号通路，从而可能延缓脓毒症的进展。
Sepsis is a fetal immunological disorder and its complication worsens in the patients with hemodialysis which may increase the risk of death. In the present study, we aimed to investigate the effect of homeodomain-interacting protein kinase 3 (HIPK3) on inflammatory factors and oxidative stress markers in monocytes of rats with sepsis by regulating the c-Jun amino-terminal kinase (JNK)/c-Jun signaling pathway. A rat model of sepsis was initially established using cecal ligation and puncture (CLP) and was further identified by enlarged spleen tissues, inflammation, and oxidative stress. Monocytes were isolated from rats with CLP-induced sepsis. HIPK3 was observed to be downregulated while JUN was upregulated in monocytes from rats with CLP-induced sepsis. Furthermore, isolated monocytes were transduced with lentiviral vectors expressing HIPK3 or shRNA against HIPK3 to explore the effect of HIPK3 on viability and apoptosis of monocytes as well as inflammatory factors and oxidative stress markers. The obtained data exhibited that overexpression of HIPK3 or inhibition of the JNK signaling pathway enhanced proliferation, reduced apoptosis of monocytes, alleviated inflammation, and oxidative stress injury. Consistently, our results may provide evidence that HIPK3 could inhibit the JNK/c-Jun signaling pathway, thereby potentially retarding the progression of sepsis.