4.2 Article

MFG-E8 alleviates oxygen-glucose deprivation-induced neuronal cell apoptosis by STAT3 regulating the selective polarization of microglia

Journal

INTERNATIONAL JOURNAL OF NEUROSCIENCE
Volume 131, Issue 1, Pages 15-24

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/00207454.2020.1732971

Keywords

Ischemic stroke; microglia polarization; MFG-E8; STAT3

Categories

Funding

  1. Natural Science Foundation of Guangdong Province [2016A030313314]
  2. Medical Scientific Research Foundation of Guangdong Province [201711385910393]
  3. Guangdong Medical Science and Technology Research Fund [B2018105]

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The study revealed that MFG-E8 reduced neuronal cell apoptosis by promoting M2 polarization of microglia, potentially providing a novel mechanism for ischemic stroke.
Background: Ischemic stroke is a complex pathological process, involving inflammatory reaction, energy metabolism disorder, free radical injury, cell apoptosis and other aspects. Accumulating evidences have revealed that MFG-E8 had a protective effect on multiple organ injuries. However, the comprehensive function and mechanism of MFG-E8 in ischemic brain remain largely unclear. Methods: BV-2 cells were treated with recombinant murine MFG-E8 (rmMFG-E8) or/and Colivelin TFA after exposing for 4 h with oxygen glucose deprivation (OGD). Cell viability and apoptosis were assessed by MTT assay and Flow cytometry. RT-qPCR and Western blot assays were applied to examine the expression levels of MFG-E8, apoptosis-related proteins and M1/M2 polarization markers. Results: Our results demonstrated that OGD significantly inhibited microglial viability and facilitated apoptosis. In addition, we found that OGD downregulated MFG-E8 expression, and MFG-E8 inhibited OGD-induced microglial apoptosis and promoted microglial M2 polarization. In terms of mechanism, we proved that MFG-E8 regulated OGD-induced microglial M1/M2 polarization by inhibiting p-STAT3 and SOCS3 expressions, which was reversed by STAT3 activator (Colivelin TFA). Finally, we verified MFG-E8 alleviated OGD-induced neuronal cell apoptosis by M2 polarization of BV-2 cells. Conclusions: We demonstrated that MFG-E8 reduced neuronal cell apoptosis by enhancing activation of microglia via STAT3 signaling. Therefore, we suggested that MFG-E8 might provide a novel mechanism for ischemic stroke.

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