miR-30c-5p Alleviated Pyroptosis During Sepsis-Induced Acute Kidney Injury via Targeting TXNIP.
miR-30c-5p Alleviated Pyroptosis During Sepsis-Induced Acute Kidney Injury via Targeting TXNIP.
复制标题
miR-30 c-5 p通过靶向TXNIP减轻脓毒症诱导的急性肾损伤期间的焦亡
DOI：
10.1007/s10753-020-01323-9
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发表时间：
2021-03
期刊：
影响因子：
5.1
通讯作者：
Yu Q
中科院分区：
文献类型：
--
作者：
Li X;Yao L;Zeng X;Hu B;Zhang X;Wang J;Zhu R;Yu Q
脓毒症引起的急性肾损伤（萨基）是住院患者的常见并发症，常导致不可接受的死亡率。有效的治疗或诊断生物标志物有限，潜在的机制仍不清楚。miR-30 c-5 p被认为是肾脏疾病的关键介质，在萨基患者中异常降低，但其机制尚不清楚。为此，本研究研究探讨了miR-30 c-5 p在萨基中的作用。在这里，我们首次证实了miR-30 c-5 p表达在我们的脓毒症模型中降低，并且与NLRP 3/caspase-1介导的焦亡的激活相关。过表达miR-30 c-5 p可通过抑制HK-2细胞凋亡减轻肾损伤。此外，我们确定TXNIP是miR-30 c-5 p的直接靶点。miR-30 c-5 p的上调抑制了TXNIP的表达，TXNIP抑制了NLRP 3、ASC和caspase-1的表达，以及炎性细胞因子的分泌。总之，我们的数据表明，miR-30 c-5 p通过TXNIP负性控制NLRP 3信号通路相关的焦亡和脓毒症诱导的损伤，表明该轴可能是萨基患者的积极治疗靶点。
Sepsis-induced acute kidney injury (SAKI) is a common complication of hospitalized patients, often leading to unacceptable mortality. Limited effective treatment or diagnosis biomarkers are available and the underlying mechanism remains unclear. The miR-30c-5p is considered as a critical mediator of kidney diseases and aberrantly decreased in patients with SAKI, while the mechanism is still unclear. For this purpose, the role of miR-30c-5p in SAKI has been investigated in this study. Here, we first confirmed that miR-30c-5p expression decreased in our septic models and was associated with the activation of NLRP3/caspase-1-mediated pyroptosis. Overexpression of miR-30c-5p alleviated the kidney injury via suppressing HK-2 cell pyroptosis. Furthermore, we identified that TXNIP was a direct target of miR-30c-5p. Upregulation of miR-30c-5p repressed the expression of TXNIP, which inhibited NLRP3, ASC, and caspase-1 expression, as well as secretion of inflammatory cytokines. In conclusion, our data suggested that miR-30c-5p negatively controlled the NLRP3 signal pathway-related pyroptosis and sepsis-induced injury via TXNIP, indicating that this axis might be a positive therapeutic target for the patient with SAKI.
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