The protective role of miR-223 in sepsis-induced mortality.
The protective role of miR-223 in sepsis-induced mortality.
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DOI：
10.1038/s41598-020-74965-2
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发表时间：
2020-10-19
影响因子：
4.6
通讯作者：
Xie L
中科院分区：
文献类型：
--
作者：
Liu D;Wang Z;Wang H;Ren F;Li Y;Zou S;Xu J;Xie L
淋巴细胞凋亡在脓毒症免疫功能障碍中起重要作用。我们研究了miR-223在细胞增殖和凋亡中的作用，以确定脓毒症中潜在的靶向下游蛋白。我们从中国人民解放军总医院招募了143例脓毒症患者和44例健康对照。使用流式细胞术从新鲜外周血中分选单核细胞、淋巴细胞和中性粒细胞。使用miR-223模拟物和抑制剂瞬时转染Jurkat T细胞。使用定量逆转录酶-聚合酶链反应（qRT-PCR）来评估细胞中miRNA的表达。进行蛋白质印迹分析以测量蛋白质表达。采用流式细胞术（FCM）和末端脱氧核苷酸转移酶缺口末端标记（TUNEL）检测细胞周期和凋亡。存活组中miR-223的表达显著高于非存活组。多元线性回归分析显示，SOFA评分与miR-223和单核细胞计数呈负相关，β系数（95%CI）分别为− 0.048（− 0.077，− 0.019）和− 47.707（− 83.871，− 11.543）。miR-223表达与淋巴细胞凋亡率呈负相关。miR-223模拟物组的细胞凋亡率显著低于阴性对照组，在miR-223抑制剂组中观察到不良结果。我们还发现，miR-223增强Jurkat T细胞的增殖，抑制miR-223对G1/S转换具有抑制作用。我们的结论是，miR-223可以作为脓毒症的保护因子，通过减少细胞凋亡和增强细胞增殖的淋巴细胞与FOXO 1相互作用。潜在的下游分子是HSP 60、HSP 70和HTRA。
Lymphocyte apoptosis appears to play an important role in immunodysfunction in sepsis. We investigated the role of miR-223 in cell proliferation and apoptosis to identify potential target downstream proteins in sepsis. We recruited 143 patients with sepsis and 44 healthy controls from the Chinese PLA General Hospital. Flow cytometry was used to sort monocytes, lymphocytes, and neutrophils from fresh peripheral blood. A miR-223 mimic and inhibitor were used for transient transfection of Jurkat T cells. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to assess expression of the miRNAs in cells. Western blot analysis was performed to measure protein expression. We evaluated the cell cycle and apoptosis by using flow cytometry (FCM) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Expression of miR-223 was significantly higher in the survivor group than in the nonsurvivor group. Multiple linear regression analysis revealed that SOFA scores correlated negatively with miR-223 and monocyte counts, with β coefficients (95% CI) of − 0.048 (− 0.077, − 0.019) and − 47.707 (− 83.871, − 11.543), respectively. miR-223 expression also correlated negatively with the percentage of apoptosis in lymphocytes. The rate of apoptosis in the miR-223 mimic group was significantly lower than that of the negative control, with an adverse outcome observed in the miR-223 inhibitor group. We also found that miR-223 enhanced the proliferation of Jurkat T cells and that inhibiting miR-223 had an inhibitory effect on the G1/S transition. We conclude that miR-223 can serve as a protective factor in sepsis by reducing apoptosis and enhancing cell proliferation in lymphocytes by interacting with FOXO1. Potential downstream molecules are HSP60, HSP70, and HTRA.
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影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
DOI：
10.1186/s13054-015-1032-4
发表时间：
2015-09-11
期刊：
Critical care (London, England)
影响因子：
--
作者：
Zhang X;Liu D;Liu YN;Wang R;Xie LX
通讯作者：
Xie LX
在败血症相关的miRNA靶基因编码的败血症患者中鉴定了四种新型血清蛋白生物标志物。
DOI：
10.1042/cs20130301
发表时间：
2014-06
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Wang HJ;Wang BZ;Zhang PJ;Deng J;Zhao ZR;Zhang X;Xiao K;Feng D;Jia YH;Liu YN;Xie LX
通讯作者：
Xie LX
影响因子：
11.8
作者：
Lodise, Thomas P.;McKinnon, Peggy S.;Rybak, Michael J.
通讯作者：
Rybak, Michael J.