Upregulation of lncRNA NONRATG019935.2 suppresses the p53-mediated apoptosis of renal tubular epithelial cells in septic acute kidney injury.
Upregulation of lncRNA NONRATG019935.2 suppresses the p53-mediated apoptosis of renal tubular epithelial cells in septic acute kidney injury.
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lncRNA NONRATG019935.2的上调抑制脓毒症急性肾损伤中p53介导的肾小管上皮细胞凋亡
DOI：
10.1038/s41419-021-03953-9
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发表时间：
2021-11-01
影响因子：
9
通讯作者：
Yu YS
中科院分区：
文献类型：
--
作者：
Ding Y;Zhou DY;Yu H;Zhu T;Guo F;He Y;Guo XL;Lin YJ;Liu YJ;Yu YS
尽管越来越多的证据已经证实肾小管上皮细胞（RTEC）的凋亡是脓毒性急性肾损伤（阿基）的发生和发展的关键因素，但是在脓毒性阿基期间RTEC凋亡上调的病理机制尚不完全清楚。在这项研究中，通过盲肠结扎穿刺程序或脂多糖（LPS）注射诱导脓毒性阿基大鼠模型。使用RNA测序确定脓毒症阿基大鼠模型中四种差异表达的长非编码RNA（DE-Lnc），并通过qRT-PCR验证。在四种DE-Lnc中，lncRNA NONRATG019935.2（9935）的表达水平在脓毒症阿基大鼠和LPS处理的NRK-52 E细胞（大鼠RTEC细胞系）中均表现出最显著的降低。9935的过表达抑制LPS处理的NRK-52 E细胞中的细胞凋亡和p53蛋白水平，并在脓毒症阿基大鼠模型中延迟脓毒症阿基的发展。在机制上，9935通过限制人抗原R（HuR）与RTEC中Tp 53 mRNA的3′UTR区域的结合来降低HuR介导的Tp 53 mRNA稳定性。HuR的过表达消除了pcDNA-9935对LPS诱导的NRK-52 E和大鼠原代RTECs凋亡的抑制作用。总之，9935通过抑制p53介导的RTEC细胞凋亡在脓毒症阿基中发挥作用，而9935的这种重要作用依赖于其对HuR介导的Tp 53 mRNA稳定性的破坏作用。
Although increasing evidence has confirmed that the apoptosis of renal tubular epithelial cells (RTECs) is a crucial contributor to the onset and development of septic acute kidney injury (AKI), the pathological mechanism by which RTEC apoptosis is upregulated during septic AKI is not entirely clear. In this study, a rat model of septic AKI was induced by a cecal ligation puncture procedure or lipopolysaccharide (LPS) injection. Four differentially expressed long noncoding RNAs (DE-Lncs) in the rat model of septic AKI were determined using RNA-sequencing and verified by qRT-PCR. Among the four DE-Lncs, the expression level of lncRNA NONRATG019935.2 (9935) exhibited the most significant reduction in both septic AKI rats and LPS-treated NRK-52E cells (a rat RTEC line). The overexpression of 9935 suppressed cell apoptosis and p53 protein level in LPS-treated NRK-52E cells, and retarded septic AKI development in the rat model of septic AKI. Mechanistically, 9935 decreased the human antigen R (HuR)-mediated Tp53 mRNA stability by limiting the combination of HuR and the 3′UTR region of Tp53 mRNA in RTECs. The overexpression of HuR abrogated the inhibitory effect of pcDNA-9935 on the LPS-induced apoptosis of NRK-52E and rat primary RTECs. In conclusion, 9935 exerts its role in septic AKI by suppressing the p53-mediated apoptosis of RTECs, and this essential role of 9935 relies on its destructive effect on HuR-mediated Tp53 mRNA stability.
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DOI：
10.31491/apt.2020.03.009
发表时间：
2020
期刊：
Aging pathobiology and therapeutics
影响因子：
--
作者：
Roman MG;Flores LC;Cunningham GM;Cheng C;Dube S;Allen C;Van Remmen H;Bai Y;Hubbard GB;Saunders TL;Ikeno Y
通讯作者：
Ikeno Y
DOI：
10.2183/pjab.94.017
发表时间：
2018
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Mino T;Takeuchi O
通讯作者：
Takeuchi O
DOI：
10.1007/978-981-10-5203-3_2
发表时间：
2017-01-01
期刊：
LONG NON CODING RNA BIOLOGY
影响因子：
--
作者：
Akhade, Vijay Suresh;Pal, Debosree;Kanduri, Chandrasekhar
通讯作者：
Kanduri, Chandrasekhar
影响因子：
4.3
作者：
Vaseva, Angelina V.;Moll, Ute M.
通讯作者：
Moll, Ute M.
LncRNA-SARCC 通过改变雄激素受体 (AR)/miRNA-143-3p 信号抑制肾细胞癌 (RCC) 进展
影响因子：
12.4
作者：
Zhai, Wei;Sun, Yin;Chang, Chawnshang
通讯作者：
Chang, Chawnshang