M2 Microglia-Derived Exosomal MiR-144-5p Attenuates White Matter Injury in Preterm Infants by Regulating the PTEN/AKT Pathway Through KLF12

Overview

Journal Mol Biotechnol

Publisher Springer

Date 2025 Jan 22

PMID 39841378

Authors

Zhaokui Zhu

Meng Meng

Sisi Mo

Xinyu Wang

Lixing Qiao

Affiliations

Soon will be listed here.

Abstract

Perinatal white matter injury (WMI), which is prevalent in premature infants, involves M2 microglia affecting oligodendrocyte precursor cells (OPCs) through exosomes, promoting OPC growth and reducing WMI. The molecular mechanism of WMI remains unclear, and this study explored the role of M2 microglia-derived exosomes in WMI. A tMCAO rat model was constructed to simulate WMI characteristics in vivo. Cresyl violet staining, neurobehavioral tests, rotarod tests, immunofluorescence and immunochemistry were used to assess the role of exos-derived miR-144-5p in pathological and neurological changes in rats. OGD/R cellular models were constructed to mimic WMI characteristics in vitro. CCK-8, TUNEL, Western blotting and immunofluorescence were used to assess the role of exos-derived miR-144-5p in OPC phenotypes. Rescue assays were used to assess the role of the PTEN/AKT pathway in miR-144-5p-mediated OPC phenotypes. Bioinformatics and mechanistic experiments were used to assess the association of PTEN or KLF12 with miR-144-5p in OPCs. M2-Exos suppressed cerebral injury and facilitated demyelination repair in rats post WMI. M2-Exos suppressed OGD/R-stimulated OPC apoptosis and facilitated OGD/R-stimulated OPC differentiation. M2-Exo-derived miR-144-5p suppressed OGD/R-stimulated OPC apoptosis and facilitated OGD/R-stimulated OPC differentiation. M2-Exo-derived miR-144-5p suppressed cerebral injury and facilitated demyelination repair in rats post WMI. MiR-144-5p suppressed OGD/R-stimulated OPC apoptosis and facilitated OGD/R-stimulated OPC differentiation through PTEN downregulation. MiR-144-5p targeted the KLF12 3'UTR to repress PTEN transcription in OPCs. M2 microglia secrete miR-144-5p to reduce WMI by targeting KLF12 in OPCs, inhibiting PTEN/AKT pathway activity, and offering potential targeted therapeutic insights for WMI.

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