Related Experiment Video
Updated: Feb 2, 2026

Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke
Published on: January 3, 2025
MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke
Ting Zhang1, Hongmei Wang2, Qiang Li3
1Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China549832649@qq.com.
Background/Aims:
This study focused on evaluating the effect of MALAT1 and MDM2 on ischemic stroke through regulation of the p53 signaling pathway.
Materials:
Bioinformatics analysis was performed to identify abnormally expressed lncRNAs, mRNAs and their associated pathways. Oxygen-glucose deprivation/reoxygenation (OGD/R) in cells and middle cerebral artery occlusion/reperfusion (MCAO/R) in mice were performed to simulate an ischemic stroke environment. Western blot and qRT-PCR were used to examine lncRNA expression and mRNA levels. Fluorescence in situ hybridization (FISH) LncRNA was used to locate mRNA. MTT and flow cytometry were performed to examine cell proliferation and apoptosis. Finally, immunohistochemistry was used to observe the expression of genes in vivo.
Results:
MALAT1 and MDM2, which exhibit strong expression in stroke tissues, were subjected to bioinformatics analysis, and the p53 pathway was chosen for further study. MALAT1, MDM2 and p53 signaling pathway-related proteins were all up regulated in OGD/R cells. Furthermore, Malat1, Mdm2 and p53 pathway related-proteins were also up regulated in MCAO/R mice. Both MALAT1 and MDM2 were localized in the nuclei. Down regulation of MALAT1 and MDM2 enhanced cell proliferation ability and reduced apoptosis, resulting in decreased infarct size in MCAO/R brains.
Conclusion:
These results indicate that MALAT1/MDM2/p53 signaling pathway axis may provide more effective clinical therapeutic strategy for patients with ischemic stroke.
Insights
This study investigated MALAT1 and MDM2's role in ischemic stroke via the p53 pathway. Targeting MALAT1/MDM2 reduced cell death and infarct size, suggesting a new therapeutic strategy.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- Ischemic stroke is a leading cause of death and disability.
- The p53 signaling pathway plays a critical role in cellular responses to stress.
- Long non-coding RNAs (lncRNAs) and their involvement in stroke pathogenesis are increasingly recognized.
Purpose of the Study:
- To evaluate the effect of MALAT1 and MDM2 on ischemic stroke.
- To elucidate the regulatory role of MALAT1 and MDM2 in the p53 signaling pathway.
- To explore the therapeutic potential of targeting the MALAT1/MDM2/p53 axis in ischemic stroke.
Main Methods:
- Bioinformatics analysis to identify dysregulated lncRNAs, mRNAs, and pathways.
- In vitro (Oxygen-glucose deprivation/reoxygenation) and in vivo (middle cerebral artery occlusion/reperfusion) models of ischemic stroke.
- Quantitative real-time PCR (qRT-PCR), Western blot, fluorescence in situ hybridization (FISH), MTT assay, flow cytometry, and immunohistochemistry were employed.
Main Results:
- MALAT1 and MDM2 were found to be upregulated in ischemic stroke tissues and models.
- The MALAT1/MDM2/p53 signaling pathway was activated in response to ischemic conditions.
- Downregulation of MALAT1 and MDM2 promoted cell proliferation, reduced apoptosis, and decreased infarct size in a mouse model of ischemic stroke.
Conclusions:
- The MALAT1/MDM2/p53 signaling pathway axis is implicated in the pathogenesis of ischemic stroke.
- Targeting MALAT1 and MDM2 demonstrates a neuroprotective effect, reducing stroke-induced brain damage.
- This pathway represents a promising therapeutic target for clinical intervention in ischemic stroke patients.
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