Ma Piyong, Zhang Chunmei, Huo Pengfei, Li Yan, Yang Hailing
Intensive Care Unit of Emergency Department, The Third Hospital of Jilin University, Changchun, Jilin, China.
Emergency Department, The Third Hospital of Jilin University, Changchun, Jilin, China.
J Biochem Mol Toxicol. 2020 Sep;34(9):e22540. doi: 10.1002/jbt.22540. Epub 2020 Jun 25.
Acute kidney injury (AKI) is one of the most common and serious complications in the development of sepsis. Many microRNAs are closely related to the occurrence, development, and prognosis of sepsis AKI (but the effect and mechanism of miR-152-3p in it is unclear). Meanwhile, the ERBB receptor feedback inhibitor 1 (ERRFI1) has a negative regulatory effect on signal transducer and activator of transcription 3 (STAT3) phosphorylation on uterine epithelial cells. But, the relationship between miR-152-3p and renal function, inflammatory factors, prognosis in AKI, and the mechanism is not clear. Analyzing sepsis-induced AKI rats and the cell model, our results revealed that miR-152-3p was upregulated in septic AKI patients and positively correlated with serum creatinine, urea nitrogen, interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). Downregulation of miR-152-3p with the inhibitor could dramatically attenuate caspase-3, bromodeoxyuridine and IL-1β, and TNF-α in the AKI rats' model. Furthermore, downregulation of miR-152-3p attenuated lipopolysaccharide-induced apoptosis and inflammatory response in HK-2 and HEK293 cells. To further explore the mechanisms, we found ERRFI1 was appreciably downregulated and STAT3 was upregulated in AKI, whereas ERRFI1 was radically upregulated and STAT3 was greatly downregulated after the addition of miR-152-3p inhibitor, no matter in vivo or in vitro. Summarily, our study confirmed that miR-152-3p could promote the expression of STAT3 by targeting ERRFI1, aggravate cell apoptosis and inflammatory response, and thereby aggravate kidney injury in sepsis AKI.
急性肾损伤（AKI）是脓毒症发展过程中最常见且严重的并发症之一。许多微小RNA与脓毒症AKI的发生、发展及预后密切相关（但miR-152-3p在其中的作用及机制尚不清楚）。同时，表皮生长因子受体反馈抑制因子1（ERRFI1）对子宫上皮细胞中信号转导与转录激活因子3（STAT3）的磷酸化具有负调控作用。但是，miR-152-3p与AKI患者肾功能、炎症因子、预后之间的关系及其机制尚不清楚。通过分析脓毒症诱导的AKI大鼠及细胞模型，我们的研究结果显示，miR-152-3p在脓毒症AKI患者中表达上调，且与血清肌酐、尿素氮、白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）呈正相关。使用抑制剂下调miR-152-3p可显著减轻AKI大鼠模型中的半胱天冬酶-3、溴脱氧尿苷、IL-1β及TNF-α水平。此外，下调miR-152-3p可减轻脂多糖诱导的HK-2和HEK293细胞凋亡及炎症反应。为进一步探究其机制，我们发现，无论在体内还是体外，AKI中ERRFI1明显下调而STAT3上调，而添加miR-152-3p抑制剂后，ERRFI1显著上调而STAT3大幅下调。总之，我们的研究证实，miR-152-3p可通过靶向ERRFI1促进STAT3表达，加重细胞凋亡和炎症反应，从而加重脓毒症AKI中的肾损伤。
