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Plk2 Regulated by miR-128 Induces Ischemia-Reperfusion Injury in Cardiac Cells
Duo Zhao1, Edward Shun2, Fengjun Ling2
1Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, China; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada; Department of Cardiovascular Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
Abstract:
Ischemia-reperfusion (I/R) injury occurs during cardiac surgery and is the major factor leading to heart dysfunction and heart failure. Our previous study showed that gene and microRNA expression profiles are altered in heart grafts with extended I/R injury. In this study, we, for the first time, demonstrated that I/R injury upregulates the expression of Polo-like kinase 2 (Plk2) but decreases miR-128 expression in heart cells both in vitro and in vivo. Silencing Plk2 using small interfering RNA (siRNA) protects cells from Antimycin A-induced cell apoptosis/death. Silencing Plk2 also decreases phosphorylated p65 expression but increases Angiopoietin 1 expression. In addition, Plk2 is negatively regulated by miR-128. miR-128 exerts a protective effect on cell apoptosis similar to Plk2 siRNA in response to I/R stress. Methylation inhibitor 5-azacytidine (5-AZ) increases the expression of miR-128 and subsequently reduces Plk2 expression and cell apoptosis. In conclusion, this study demonstrated that Plk2 regulated by miR-128 induces cell apoptosis/death in response to I/R stress through activation of the nuclear factor κB (NF-κB) signal pathway. miR-128 and Plk2 are new targets for preventing cardiac I/R injury or oxidative stress-mediated injury.
Insights
Ischemia-reperfusion injury increases Polo-like kinase 2 (Plk2) and decreases miR-128 in heart cells. Targeting Plk2 or enhancing miR-128 protects against cardiac injury by inhibiting the NF-κB pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Stress Response
Background:
- Ischemia-reperfusion (I/R) injury is a primary cause of heart dysfunction and failure post-cardiac surgery.
- Altered gene and microRNA expression profiles are observed in heart grafts experiencing extended I/R injury.
Purpose of the Study:
- To investigate the roles of Polo-like kinase 2 (Plk2) and miR-128 in cardiac I/R injury.
- To elucidate the regulatory relationship between Plk2 and miR-128 in the context of I/R stress.
Main Methods:
- Investigated Plk2 and miR-128 expression in heart cells in vitro and in vivo under I/R conditions.
- Utilized small interfering RNA (siRNA) to silence Plk2 and assessed its effects on cell apoptosis, phosphorylated p65, and Angiopoietin 1.
- Examined the regulatory mechanism of miR-128 on Plk2 and the impact of 5-azacytidine (5-AZ) on miR-128 and Plk2 expression.
Main Results:
- I/R injury upregulated Plk2 and downregulated miR-128 in heart cells.
- Plk2 silencing protected cells from apoptosis, reduced phosphorylated p65, and increased Angiopoietin 1.
- miR-128 negatively regulated Plk2, and its upregulation mimicked the protective effects of Plk2 silencing against I/R stress.
- 5-AZ treatment increased miR-128, subsequently decreasing Plk2 and cell apoptosis.
Conclusions:
- Plk2, regulated by miR-128, induces apoptosis in response to I/R stress via the NF-κB pathway.
- miR-128 and Plk2 represent novel therapeutic targets for mitigating cardiac I/R injury and oxidative stress-mediated damage.
