Up-regulating microRNA-214-3p relieves hypoxic-ischemic brain damage through inhibiting TXNIP expression

Mol Cell Biochem. 2023 Mar;478(3):597-608. doi: 10.1007/s11010-022-04530-0. Epub 2022 Aug 18.

Abstract

A list of microRNAs (miRs) has been referred to involve in the development of hypoxic-ischemic brain damage (HIBD). Based on that, we probed the concrete role of miR-214-3p regulating thioredoxin-interacting protein (TXNIP) in the illness. A neonatal HIBD mouse model was established using the Rice-Vannucci method, followed by measurements of miR-214-3p and TXNIP levels in brain tissues. After modeling, mice were given brain injection of the compounds that could alter miR-214-3p and TXNIP expression. Afterward, neurological function, neuronal inflammation, neuronal apoptosis, neuron morphology, and the number of Nissl body were assessed in HIBD mice. The binding of miR-214-3p to TXNIP was analyzed. Lower miR-214-3p and higher TXNIP were analyzed in brain tissues of mice with HIBD. Up-regulating miR-214-3p or depleting TXNIP improved neurological function, reduced neuronal inflammation and neuronal apoptosis, attenuated morphological damage of neurons, and increased the number of Nissl bodies in mice with HIBD. TXNIP was targeted by miR-214-3p and overexpressing TXNIP reversed the therapeutic effect of miR-214-3p on HIBD mice. It is noted that promotion of miR-214-3p relieves HIBD in mice through inhibiting TXNIP expression.

Keywords: Hypoxic–ischemic brain damage; MicroRNA-214-3p; Neurological function; Neuronal apoptosis; Nissl body; Thioredoxin-interacting protein.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Brain / metabolism
  • Carrier Proteins / metabolism
  • Hypoxia-Ischemia, Brain* / metabolism
  • Mice
  • MicroRNAs* / metabolism
  • Thioredoxins / metabolism

Substances

  • MicroRNAs
  • Txnip protein, mouse
  • Carrier Proteins
  • Thioredoxins
  • Mirn214 microRNA, mouse