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miR-21 regulates ischemic neuronal injury via the p53/Bcl-2/Bax signaling pathway
Honglin Yan1, Wenxian Huang1, Jie Rao1
1Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China.
Abstract:
Focal cerebral ischemia leads to a large number of neuronal apoptosis, and secondary neuronal death is the main cause of cerebral infarction. MicroRNA-21 (miR-21) has been shown to be a strong anti-apoptosis and pro-survival factor in ischemia. However, the precise mechanism of miR-21 in ischemic neuroprotection remains largely unknown. In this study, miR-21 was down-regulated while p53 was up-regulated following ischemia in vitro and in vivo. Overexpression of miR-21 in vitro and in vivo substantially inhibited the expression of p53 following ischemia, while inhibition of miR-21 in vitro and in vivo promoted p53 expression following ischemia. Moreover, the miR-21/p53 axis regulated the expression of Bcl-2/Bax and abolished OGD/R-induced neuronal injury in vitro. Furthermore, overexpression of miR-21 in vivo reduced neuronal death, protected against ischemic damage, and improved neurological functions by inhibiting p53/Bcl-2/Bax signaling, while inhibition of miR-21 enhanced the p53/Bcl-2/Bax signaling and aggravated the ischemic neuronal injury in vivo. Our data uncover a novel mechanism of miR-21 in regulating cerebral ischemic neuronal injury by inhibiting p53/Bcl-2/Bax signaling pathway, which suggests that miR-21/p53 may be attractive therapeutic molecules for treatment of ischemic stroke.
Insights
MicroRNA-21 (miR-21) protects neurons from ischemic injury by inhibiting p53. This study reveals miR-21/p53 signaling as a novel therapeutic target for ischemic stroke, reducing neuronal death and improving function.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Focal cerebral ischemia causes significant neuronal apoptosis, leading to cerebral infarction.
- MicroRNA-21 (miR-21) is recognized as a neuroprotective factor against ischemia, but its mechanism is unclear.
- Understanding miR-21's role is crucial for developing treatments for ischemic stroke.
Purpose of the Study:
- To elucidate the precise mechanism of miR-21 in ischemic neuroprotection.
- To investigate the relationship between miR-21 and p53 in the context of cerebral ischemia.
- To explore the therapeutic potential of the miR-21/p53 axis in ischemic stroke.
Main Methods:
- Investigated miR-21 and p53 expression levels in vitro and in vivo following ischemia.
- Manipulated miR-21 levels (overexpression and inhibition) to assess effects on p53 expression and neuronal injury.
- Analyzed the regulation of Bcl-2/Bax signaling pathway and its impact on neuronal apoptosis and ischemic damage.
Main Results:
- miR-21 was downregulated while p53 was upregulated post-ischemia.
- miR-21 overexpression inhibited p53, while miR-21 inhibition promoted p53 expression.
- The miR-21/p53 axis modulated Bcl-2/Bax expression, mitigating OGD/R-induced neuronal injury and improving outcomes in vivo.
Conclusions:
- miR-21 protects against cerebral ischemic neuronal injury by inhibiting the p53/Bcl-2/Bax signaling pathway.
- The miR-21/p53 axis represents a novel therapeutic target for ischemic stroke.
- Targeting miR-21/p53 may offer a promising strategy for neuroprotection and functional recovery after stroke.
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