MicroRNA-25-5p negatively regulates TXNIP expression and relieves inflammatory responses of brain induced by lipopolysaccharide

Sci Rep. 2022 Oct 26;12(1):17915. doi: 10.1038/s41598-022-21169-5.

Abstract

Sepsis is one of the most common causes of death in patients suffering from severe infection or injury. Currently, a specific effective therapy remains to be established. In the present study, miR-25-5p, miR-105, miR-106b-5p, miR-154-3p, miR-20b-5p, miR-295-3p, miR-291-3p, miR-301b, miR-352, and miR-93-5p were predicted to target TXNIP mRNA from the databases of miRDB, Targetscan, and microT-CDS. The luciferase reporter assay confirmed that miR-25-5p negatively regulates TXNIP expression. The ELISA analyses and western blotting demonstrated that miR-25-5p downregulated the production of IL-1β, IL-6, IL-8, and TNF-α in lipopolysaccharide (LPS)-stimulated cells or rats, as well as the protein levels of TXNIP, NLRP3, and cleaved caspase-1. In addition, miR-25-5p increased the cell viability and decreased the apoptosis in LPS-stimulated CTX TNA2 cells and reduced the abnormal morphology of the brain in LPS-stimulated rats. Besides, miR-25-5p decreased the relative mean fluorescence intensity of DCF in LPS-stimulated CTX TNA2 cell, apoptosis, and protein levels of MnSOD and catalase in LPS-stimulated brains. These findings indicate that miR-25-5p downregulated LPS-induced inflammatory responses, reactive oxygen species production, and brain damage, suggesting that miR-25-5p is a candidate treatment for septic encephalopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Brain / metabolism
  • Caspases / metabolism
  • Catalase / metabolism
  • Cell Cycle Proteins / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Lipopolysaccharides* / toxicity
  • MicroRNAs* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • RNA, Messenger / pharmacology
  • Rats
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Lipopolysaccharides
  • Catalase
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Tumor Necrosis Factor-alpha
  • Reactive Oxygen Species
  • Interleukin-6
  • Interleukin-8
  • MicroRNAs
  • RNA, Messenger
  • Caspases
  • Cell Cycle Proteins
  • MIRN25 microRNA, rat
  • Mirn93 microRNA, rat