miR-128-3p Inhibits NRP1 Expression and Promotes Inflammatory Response to Acute Kidney Injury in Sepsis
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ORIGINAL ARTICLE
miR-128-3p Inhibits NRP1 Expression and Promotes Inflammatory Response to Acute Kidney Injury in Sepsis Lin Wang ,1,3 Kai Wang,1 and Zhengyun Tian2
Abstract— 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-α, IL-1 β, 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-α, IL-6, and IL-1β; 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. KEY WORDS: miR-128-3p; NPR1; acute kidney injury; sepsis; inflammatory response.
INTRODUCTION
1
Department of ICU, ZiBo Central Hospital, 54 Gongqingtuan Road, Zhangdian District, Zibo, Shandong, China 2 Department of ICU, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Lixia District, Jinan, Shandong, China 3 To whom correspondence should be addressed at Department of ICU, ZiBo Central Hospital, 54 Gongqingtuan Road, Zhangdian District, Zibo, Shandong, China. E-mail: [email protected]
Sepsis, also known as systemic inflammatory response syndrome, is characterized by tissue damage caused by viral, bacterial, and fungal infections and results in multiple organ failure and even death. The kidney is one of the main organs of infection and damage [1]. Acute kidney injury is one of the most common complications of sepsis [2]. More than 50% of patients with sepsis are diagnosed with acute kidney injury, and these patients have
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Wang, Wang, and Tian higher mortality rate than patients with non-acute k
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