RANTES mediates kidney ischemia reperfusion injury through a possible role of HIF-1α and LncRNA PRINS.
RANTES mediates kidney ischemia reperfusion injury through a possible role of HIF-1α and LncRNA PRINS.
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DOI：
10.1038/srep18424
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发表时间：
2016-01-04
影响因子：
4.6
通讯作者：
Li CY
中科院分区：
文献类型：
--
作者：
Yu TM;Palanisamy K;Sun KT;Day YJ;Shu KH;Wang IK;Shyu WC;Chen P;Chen YL;Li CY
RANTES（调节正常 T 细胞表达和分泌的激活）在许多临床情况下招募循环白细胞并增强炎症反应。缺血再灌注损伤 (IRI) 中的炎症反应显着影响急性肾损伤 (AKI) 的不良后果，而浸润免疫细胞是 AKI 的重要介质。然而，RANTES在AKI中的意义以及缺氧诱导的LncRNA是否参与AKI的调节过程尚不清楚。在这里，我们发现，在肾 IRI 小鼠模型中，在野生型小鼠的肾小管细胞中观察到显着的 RANTES 表达。与野生型相比，RANTES 缺陷（RANTES−/−）小鼠通过减少急性肾小管坏死、血清肌酐水平、炎症细胞浸润和细胞因子表达而表现出更好的肾功能。在体外，我们发现RANTES的表达受到NF-κB的调节。此外，肾小管细胞在缺氧条件下表现出 LncRNA 表达失调。在 HIF-1α 依赖性 LncRNA 中，PRINS（压力诱导的银屑病易感性相关 RNA 基因）在缺氧条件下显着上调，并通过报告基因检测证实与 RANTES 具有特异性相互作用。这些观察结果首次证明肾小管细胞产生的 RANTES 是 AKI 中的关键趋化因子，并且 HIF-1α 调节的 LncRNA-PRINS 可能参与 RANTES 的产生。
RANTES (Regulated on activation, normal T-cell expressed and secreted), recruits circulating leukocytes and augments inflammatory responses in many clinical conditions. Inflammatory responses in ischemia-reperfusion injury (IRI) significantly affect the unfavorable outcomes of acute kidney injury (AKI), and that infiltrating immune cells are important mediators of AKI. However, the significance of RANTES in AKI and whether hypoxia-induced LncRNAs are involved in the regulatory process of AKI are not known. Here we show that, in the kidney IRI mice model, significant RANTES expression was observed in renal tubular cells of wild type mice. RANTES deficient (RANTES−/−) mice showed better renal function by reducing the acute tubular necrosis, serum creatinine levels, infiltration of inflammatory cells and cytokine expressions compared to wild type. In vitro, we found that RANTES expression was regulated by NF-κB. Further, renal tubular cells showed deregulated LncRNA expression under hypoxia. Among HIF-1α dependent LncRNAs, PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) was significantly up regulated in hypoxic conditions and had specific interaction with RANTES as confirmed through reporter assay. These observations show first evidence for RANTES produced by renal tubular cells act as a key chemokine in AKI and HIF-1α regulated LncRNA-PRINS might be involved in RANTES production.