标题：miR-128-3p Inhibits NRP1 Expression and Promotes Inflammatory Response to Acute Kidney Injury in Sepsis
作者：Wang, Lin; Wang, Kai; Tian, Zhengyun
作者机构：[Wang, Lin; Wang, Kai] ZiBo Cent Hosp, Dept ICU, 54 Gongqingtuan Rd, Zibo, Shandong, Peoples R China.; [Tian, Zhengyun] Shandong Univ Tradit Chinese 更多
通讯作者地址：Wang, L (corresponding author), ZiBo Cent Hosp, Dept ICU, 54 Gongqingtuan Rd, Zibo, Shandong, Peoples R China.
关键词：miR-128-3p; NPR1; acute kidney injury; sepsis; inflammatory response
摘要：The aims of this study were to find a treatment for acute kidney injury in sepsis and study the role of miR-128-3p in this process. We generated a model of septic acute kidney injury through cecal ligation and puncture (CLP) induction and screened differentially expressed microRNAs through microarray. The mechanism used by miR-128-3p in inflammatory response to septic acute kidney injury was investigated using cell transfection assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, enzyme-linked immunosorbent assay, western blot, and Dual-Luciferase Reporter Assay. miRNA microarray screening revealed that miR-128-3p was significantly upregulated in the kidneys of mice with CLP-induced septic acute kidney injury. The level of inflammatory factors TNF-alpha, IL-1 beta, and IL-6 decreased. In contrast, cell viability increased and apoptosis decreased with the addition of miR-128-3p inhibitors in TCMK-1 cells treated with lipopolysaccharide (LPS). Using bioinformatics and luciferin reporter gene experiments, we found that NRP1 is a miR-128-3p target gene. Overexpression of NRP1 in LPS-treated TCMK-1 cells decreased the expression of TNF-alpha, IL-6, and IL-1 beta; increased cell viability; and decreased apoptosis. The survival period of mice pretreated with miR-128-3p inhibitors was prolonged, infiltration of inflammatory cells into kidney tissue decreased, permeability of kidneys enhanced, and expression of inflammatory factors and renal apoptosis decreased. miR-128-3p targets NRP1 for cell degradation, promotes inflammatory cell infiltration, increases expression of inflammatory factors, decreases renal cell viability, and increases apoptosis in LPS-induced septic acute renal injury.