1. Academic Validation
  2. MircoRNA-29a in Astrocyte-derived Extracellular Vesicles Suppresses Brain Ischemia Reperfusion Injury via TP53INP1 and the NF-κB/NLRP3 Axis

MircoRNA-29a in Astrocyte-derived Extracellular Vesicles Suppresses Brain Ischemia Reperfusion Injury via TP53INP1 and the NF-κB/NLRP3 Axis

  • Cell Mol Neurobiol. 2022 Jul;42(5):1487-1500. doi: 10.1007/s10571-021-01040-3.
Xin Liu  # 1 2 Xinghua Lv  # 2 3 Zhenzhen Liu 2 Mengjie Zhang 3 Yufang Leng 4 5
Affiliations

Affiliations

  • 1 The Reproductive Medicine Center, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
  • 2 The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, China.
  • 3 Department of Anesthesiology, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou, 730000, China.
  • 4 The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, China. [email protected].
  • 5 Department of Anesthesiology, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou, 730000, China. [email protected].
  • # Contributed equally.
Abstract

Brain ischemia reperfusion injury (BIRI) is defined as a series of brain injury accompanied by inflammation and oxidative stress. Astrocyte-derived extracellular vesicles (EVs) are importantly participated in BIRI with involvement of MicroRNAs (miRs). Our study aimed to discuss the functions of miR-29a from astrocyte-derived EVs in BIRI treatment. Thus, astrocyte-derived EVs were extracted. Oxygen and glucose deprivation (OGD) cell models and BIR rat models were established. Then, cell and rat activities and pyroptosis-related protein levels in these two kinds of models were detected. Functional assays were performed to verify inflammation and oxidative stress. miR-29a expression in OGD cells and BIR rats was measured, and target relation between miR-29a and tumor protein 53-induced nuclear protein 1 (TP53INP1) was certified. Rat neural function was tested. Astrocyte-derived EVs improved miR-29a expression in N9 microglia and rat brains. Astrocyte-derived EVs inhibited OGD-induced injury and inflammation in vitro, reduced brain infarction, and improved BIR rat neural functions in vivo. miR-29a in EVs protected OGD-treated cells and targeted TP53INP1, whose overexpression suppressed the protective function of EVs on OGD-treated cells. miR-29a alleviated OGD and BIRI via downregulating TP53INP1 and the NF-κB/NLRP3 pathway. Briefly, our study demonstrated that miR-29a in astrocyte-derived EVs inhibits BIRI by downregulating TP53INP1 and the NF-κB/NLRP3 axis.

Keywords

Astrocyte; Brain ischemia reperfusion injury; Extracellular vesicles; Inflammation; Oxidative stress; TP53INP1; mircoRNA-29a.

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