Regulatory coupling between long noncoding RNAs and senescence in irradiated microglia.
Regulatory coupling between long noncoding RNAs and senescence in irradiated microglia.
复制标题
长非编码RNA与辐照小胶质细胞衰老之间的调节耦合
DOI：
10.1186/s12974-020-02001-1
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发表时间：
2020-10-28
影响因子：
9.3
通讯作者：
Yuan Y
中科院分区：
文献类型：
--
作者：
Xu A;Li R;Ren A;Jian H;Huang Z;Zeng Q;Wang B;Zheng J;Chen X;Zheng N;Zheng R;Tian Y;Liu M;Mao Z;Ji A;Yuan Y
小胶质细胞参与了放射性脑损伤（radiation-induced brain injury，RIBI）的发病机制，严重影响了患者的长期生存质量。最近，照射小胶质细胞被推测呈现出衰老样表型。长的非编码RNA（lncRNA）已被公认为调节广泛的生物过程，包括衰老，然而，它们在辐照小胶质细胞的潜在作用仍然在很大程度上uncharacterized.MethodsWe使用生物信息学和实验方法来识别和分析辐照小胶质细胞的衰老表型。Western印迹，酶联免疫吸附试验，免疫荧光，定量实时逆转录-聚合酶链反应进行澄清辐射诱导的差异表达的lncRNA（RILs）和辐射小胶质细胞衰老的独特分子特征之间的关系。RILs与受照小胶质细胞衰老表型的三个主要特征：炎症、DNA损伤反应（DDR）和代谢之间存在相互调节模式。具体而言，对于炎症，两种选定的RILs（ENSMUST 00000190863和ENSMUST 00000130679）的表达依赖于核因子κ B（NF-κB）和丝裂原活化蛋白激酶（MAPK）的主要炎症信号通路。这两种RILs可调节NF-κB/MAPK信号通路的激活和随后的炎性细胞因子分泌。对于DDR，DNA损伤的不同严重程度改变了RILs的表达谱。选定的RIL ENSMUST 00000130679促进了DDR。对于代谢，固醇调节元件结合蛋白介导的脂肪生成的阻断衰减的倍数变化的几个RILs诱导IR。ConclusionsOur研究结果表明，某些RILs相互作用与辐射小胶质细胞衰老。RILs参与了衰老过程的调控，提示RILs可能是治疗RIBI的有效干预靶点。
BackgroundMicroglia have been implicated in the pathogenesis of radiation-induced brain injury (RIBI), which severely influences the quality of life during long-term survival. Recently, irradiated microglia were speculated to present an aging-like phenotype. Long noncoding RNAs (lncRNAs) have been recognized to regulate a wide spectrum of biological processes, including senescence; however, their potential role in irradiated microglia remains largely uncharacterized.MethodsWe used bioinformatics and experimental methods to identify and analyze the senescence phenotype of irradiated microglia. Western blotting, enzyme-linked immunosorbent assays, immunofluorescence, and quantitative real-time reverse transcription-polymerase chain reaction were performed to clarify the relationship between the radiation-induced differentially expressed lncRNAs (RILs) and the distinctive molecular features of senescence in irradiated microglia.ResultsWe found that the senescence of microglia could be induced using ionizing radiation (IR). A mutual regulation mode existed between RILs and three main features of the senescence phenotype in irradiated microglia: inflammation, the DNA damage response (DDR), and metabolism. Specifically, for inflammation, the expression of two selected RILs (ENSMUST00000190863 and ENSMUST00000130679) was dependent on the major inflammatory signaling pathways of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). The two RILs modulated the activation of NF-κB/MAPK signaling and subsequent inflammatory cytokine secretion. For the DDR, differential severity of DNA damage altered the expression profiles of RILs. The selected RIL, ENSMUST00000130679, promoted the DDR. For metabolism, blockade of sterol regulatory element-binding protein-mediated lipogenesis attenuated the fold-change of several RILs induced by IR.ConclusionsOur findings revealed that certain RILs interacted with senescence in irradiated microglia. RILs actively participated in the regulation of senescence features, suggesting that RILs could be promising intervention targets to treat RIBI.
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影响因子：
10.8
作者：
Hofmann P;Sommer J;Theodorou K;Kirchhof L;Fischer A;Li Y;Perisic L;Hedin U;Maegdefessel L;Dimmeler S;Boon RA
通讯作者：
Boon RA
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
DOI：
10.1158/1078-0432.ccr-11-2903
发表时间：
2013-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Greene-Schloesser D;Moore E;Robbins ME
通讯作者：
Robbins ME
影响因子：
9.7
作者：
Azzam EI;Jay-Gerin JP;Pain D
通讯作者：
Pain D
影响因子：
64.5
作者：
Atianand MK;Hu W;Satpathy AT;Shen Y;Ricci EP;Alvarez-Dominguez JR;Bhatta A;Schattgen SA;McGowan JD;Blin J;Braun JE;Gandhi P;Moore MJ;Chang HY;Lodish HF;Caffrey DR;Fitzgerald KA
通讯作者：
Fitzgerald KA