miRNA155-5P participated in DDX3X targeted regulation of pyroptosis to attenuate renal ischemia/reperfusion injury.
miRNA155-5P participated in DDX3X targeted regulation of pyroptosis to attenuate renal ischemia/reperfusion injury.
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DOI：
10.18632/aging.204692
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发表时间：
2023-05-04
期刊：
影响因子：
5.2
通讯作者：
Leng, Yufang
中科院分区：
文献类型：
--
作者：
Zhang, Yan;Lv, Xinghua;Fan, Qian;Chen, Feng;Wan, Zhanhai;Nibaruta, Janvier;Wang, Hao;Wang, Xiaoxia;Yuan, Yuan;Guo, Wenwen;Leng, Yufang
背景资料：肾缺血再灌注损伤（IRI）通过多种因素导致肾微血管和肾小管上皮细胞的病理损伤。然而，研究miRNA 155 - 5 P是否靶向DDX 3X以减轻焦亡的研究很少。结果如下：在IRI组中，与脓毒症相关的蛋白（caspase-1、白细胞介素-1 β（IL-1β）、NOD样受体家族pyrin domain containing 3（NLRP 3）和IL-18）的表达上调。此外，与假手术组相比，IRI组中的miR-155- 5 p更高。miR-155- 5 p模拟物对DDX 3X的抑制作用大于其他组。所有H/R组的DEAD-box解旋酶3 X连锁（DDX 3X）、NLRP 3、caspase-1、IL-1β、IL-18、LDH和焦亡率均高于对照组。这些指标在miR-155- 5 p模拟物组中高于H/R和miR-155- 5 p模拟物阴性对照（NC）组。结论：目前的研究结果表明，miR-155- 5 p通过下调DDX 3X/NLRP 3/caspase-1通路减少了参与细胞凋亡的炎症。研究方法：采用小鼠IRI模型和缺氧-复氧（H/R）诱导的人近端肾小管上皮细胞（HK-2细胞）损伤模型，分析了缺氧-复氧损伤后肾脏病理变化及与细胞凋亡和DDX 3X相关因子的表达。采用实时荧光定量逆转录聚合酶链反应（RT-PCR）检测miRNAs，酶联免疫吸附试验（ELISA）检测乳酸脱氢酶活性。StarBase和荧光素酶测定检测了DDX 3X和miRNA 155 - 5 P的特异性相互作用。在IRI组中，检查了严重的肾组织损伤、肿胀和炎症。
Background: Renal ischemia/reperfusion injury (IRI) induced pathological damage to renal microvessels and tubular epithelial cells through multiple factors. However, studies investigated whether miRNA155-5P targeted DDX3X to attenuate pyroptosis were scarce. Results: The expression of pyroptosis-related proteins (caspase-1, interleukin-1β (IL-1β), NOD-like receptor family pyrin domain containing 3 (NLRP3), and IL-18) were up-regulated in the IRI group. Additionally, miR-155-5p was higher in the IRI group comparing with the sham group. The DDX3X was inhibited by the miR-155-5p mimic more than in the other groups. DEAD-box Helicase 3 X-Linked (DDX3X), NLRP3, caspase-1, IL-1β, IL-18, LDH, and pyroptosis rates were higher in all H/R groups than in the control group. These indicators were higher in the miR-155-5p mimic group than in the H/R and the miR-155-5p mimic negative control (NC) group. Conclusions: Current findings suggested that miR-155-5p decreased the inflammation involved in pyroptosis by downregulating the DDX3X/NLRP3/caspase-1 pathway. Methods: Using the models of IRI in mouse and the hypoxia-reoxygenation (H/R)-induced injury in human renal proximal tubular epithelial cells (HK-2 cells), we analyzed the changes in renal pathology and the expression of factors correlated with pyroptosis and DDX3X. Real-time reverse transcription polymerase chain reaction (RT-PCR) detected miRNAs and enzyme-linked immunosorbent assay (ELISA) was used to detect lactic dehydrogenase activity. The StarBase and luciferase assays examined the specific interplay of DDX3X and miRNA155-5P. In the IRI group, severe renal tissue damage, swelling, and inflammation were examined.
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作者：
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影响因子：
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作者：
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10.1016/j.jash.2017.10.008
发表时间：
2017-12-01
影响因子：
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作者：
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通讯作者：
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