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MicroRNA-128-3p Protects Mouse Against Cerebral Ischemia Through Reducing p38α Mitogen-Activated Protein Kinase
Guochao Mao1, Pengyu Ren1, Gang Wang1
1Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
Abstract:
The p38α, also named Mapk14, is a pro-apoptotic protein, which is reported to be downregulated 2 h after cerebral ischemia. However, little is known what causes the downregulation of p38α protein level. Here, we studied the effect of cerebral ischemia on p38α mRNA expression and p38α protein level in brain of mice. We found that p38α protein level is reduced after middle cerebral artery occlusion. However, at the meantime, p38α mRNA expression has no detectable changes, suggesting that the possible posttranscription is regulated by ischemia. To reveal the mechanism for posttranscription of p38α protein, we tested the effect of miR-128-3p. Using luciferase reporter assay, we found that miR-128-3p could directly target p38α 3'UTR. We further tested the effect of miR-128-3p on the p38α protein level. We found that miR-128-3p strongly decreased the p38α protein level in SH-SY5Y cells after the cells were transfected with miR-128-3p using lentivirus vector containing precursor its RNA sequences. We further found that inhibition of miR-128-3p enhanced the infarct volume of brain in mice. Our study thus confirms that miR-128-3p can downregulate p38α protein level through posttranscription and increase of miR-128-3p level may contribute to neuronal survival in ischemia-induced brain injury.
Insights
Cerebral ischemia downregulates p38α protein, but not mRNA. MicroRNA-128-3p targets p38α, reducing its levels and potentially protecting neurons in brain injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- p38α (Mapk14) is a pro-apoptotic protein downregulated post-cerebral ischemia.
- The mechanism causing p38α downregulation after ischemia remains unclear.
Purpose of the Study:
- Investigate the effect of cerebral ischemia on p38α mRNA and protein levels.
- Elucidate the post-transcriptional regulatory mechanism of p38α involving microRNA-128-3p.
Main Methods:
- Middle cerebral artery occlusion (MCAO) in mice to induce ischemia.
- Analysis of p38α mRNA and protein expression.
- Luciferase reporter assay to confirm microRNA-128-3p targeting of p38α 3'UTR.
- In vitro experiments using SH-SY5Y cells transfected with miR-128-3p.
- Assessment of infarct volume in mice after miR-128-3p inhibition.
Main Results:
- p38α protein levels decreased after MCAO, while mRNA levels remained unchanged.
- MicroRNA-128-3p was identified as a direct targeting molecule of p38α 3'UTR.
- Transfection with miR-128-3p significantly reduced p38α protein levels in SH-SY5Y cells.
- Inhibition of miR-128-3p led to increased infarct volume in mice.
Conclusions:
- Cerebral ischemia regulates p38α protein levels post-transcriptionally.
- MicroRNA-128-3p downregulates p38α protein expression.
- Increased miR-128-3p levels may promote neuronal survival in ischemia-induced brain injury.
