MicroRNA‐214‐5p aggravates sepsis‐related acute kidney injury in mice

• Published in: Drug development research 2022-04, Vol.83 (2), p.339-350
• Main Authors: Guo, Cheng, Ye, Fang‐Xiong, Jian, Yong‐Hong, Liu, Chun‐Hua, Tu, Zhi‐Hui, Yang, Ding‐Ping
• Format: Article
• Language: English
• Subjects: acute kidney injury; Acute Kidney Injury - genetics; Acute Kidney Injury - metabolism; Adenosine kinase; Adenosine monophosphate; AMP; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Antagomirs; Cell lines; Damage prevention; Female; Glucagon; Humans; Inflammation; Inflammation - metabolism; Kidneys; Kinases; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐214‐5p; Oxidative stress; Protein kinase; Renal function; Ribonucleic acid; RNA; Sepsis; Sepsis - complications; Sepsis - metabolism; siRNA
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21863

Acute kidney injury (AKI) is a devastating comorbidity in sepsis and correlates with a very poor prognosis and increased mortality. Currently, we use lipopolysaccharide (LPS) to establish sepsis‐related AKI and try to demonstrate the pathophysiological role of microRNA‐214‐5p (miR‐214‐5p) in this process. Mice were intravenously injected with the miR‐214‐5p agomir, antagomir or negative controls for three consecutive days and then received a single intraperitoneal injection of LPS (10 mg/kg) for 24 h to induce AKI. Besides, the Boston University mouse proximal tubular cell lines were stimulated with LPS (10 μg/ml) for 8 h to investigate the role of miR‐214‐5p in vitro. To inhibit adenosine monophosphate‐activated protein kinase (AMPK), compound C (CpC) was used in vivo. For glucagon‐like peptide‐1 receptor (GLP‐1R) silence, cells were transfected with the small interfering RNA against GLP‐1R. miR‐214‐5p level was upregulated in LPS‐treated kidneys and proximal tubular cell lines. The miR‐214‐5p antagomir reduced LPS‐induced renal inflammation and oxidative stress, thereby preventing renal damage and dysfunction. In contrast, the miR‐214‐5p agomir aggravated LPS‐induced inflammation, oxidative stress and AKI in vivo and in vitro. Mechanistically, we found that the miR‐214‐5p antagomir prevented septic AKI via activating AMPK and that CpC treatment completely abrogated its renoprotective effect in mice. Further detection showed that miR‐214‐5p directly bound to the 3′‐untranslational region of GLP‐1R to inhibit GLP‐1R/AMPK axis. Our data identify miR‐214‐5p as a promising therapeutic candidate to treat sepsis‐related AKI.