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MFG-E8 alleviates oxygen-glucose deprivation-induced neuronal cell apoptosis by STAT3 regulating the selective
Ying-Ying Fang1, Jing-Hui Zhang2,3
1Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, P.R. China.
Abstract:
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.
Insights
Milk fat globule-epidermal growth factor 8 (MFG-E8) protects against ischemic stroke by reducing microglial apoptosis and promoting M2 polarization via STAT3 signaling. This suggests MFG-E8 as a potential therapeutic target for stroke.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Ischemic stroke involves complex processes including inflammation, metabolic dysfunction, and apoptosis.
- Milk fat globule-epidermal growth factor 8 (MFG-E8) shows protective effects in various organ injuries.
- The specific role and mechanism of MFG-E8 in ischemic brain injury are not fully understood.
Purpose of the Study:
- To investigate the function and mechanism of MFG-E8 in microglial cells under oxygen-glucose deprivation (OGD) conditions.
- To determine MFG-E8's effect on microglial apoptosis and polarization.
- To elucidate the signaling pathways involved in MFG-E8's neuroprotective effects.
Main Methods:
- Utilized BV-2 microglial cells subjected to OGD.
- Treated cells with recombinant murine MFG-E8 (rmMFG-E8) and/or Colivelin TFA.
- Assessed cell viability, apoptosis, and M1/M2 polarization markers using MTT assay, flow cytometry, RT-qPCR, and Western blot.
Main Results:
- OGD reduced microglial viability, increased apoptosis, and downregulated MFG-E8 expression.
- MFG-E8 treatment inhibited OGD-induced apoptosis and promoted M2 microglial polarization.
- MFG-E8 suppressed OGD-induced M1/M2 polarization by inhibiting p-STAT3 and SOCS3, effects reversed by a STAT3 activator.
- MFG-E8 alleviated OGD-induced neuronal apoptosis through M2 polarization of microglia.
Conclusions:
- MFG-E8 reduces neuronal apoptosis in ischemic stroke models.
- This neuroprotection is mediated by enhanced microglial activation via STAT3 signaling.
- MFG-E8 represents a potential novel therapeutic strategy for ischemic stroke.
