Related Experiment Video
Updated: Aug 17, 2025
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
Chemokine receptor 7 mediates miRNA-182 to regulate cerebral ischemia/reperfusion injury in rats
Qi Wang1,2, Sifan Xu1, Bin Wang3
1Department of Neurology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China.
Aims:
Chemokine receptor 7 (CXCR7) exerts protective effects on the brain. MicroRNAs (miRNAs) are involved in cerebral ischemia/reperfusion (I/R) injury, but their involvement in CXCR7-mediated brain protection is unknown. In this study, we investigated the role of miRNAs in CXCR7-mediated brain protection.
Methods:
CXCR7 levels in peripheral blood samples from patients with acute ischemic stroke (AIS) and ischemic penumbra area brain tissues from middle cerebral artery occlusion (MCAO) rats after recanalization were measured. An miRNA microarray analysis was performed to examine the expression of miRNAs caused by CXCR7 knockdown in ischemic penumbra area brain tissue in middle cerebral artery occlusion-reperfusion rats and to predict corresponding downstream target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed the most enriched pathways. A dual-luciferase reporter assay confirmed the direct regulation of miR-182 on the target gene TCF7L2. The correlation between TCF7L2 and CXCR7/miR-182 was verified using rescue assays.
Results:
CXCR7 expression was upregulated in MCAO rats and mechanical thrombectomy patients with AIS compared to that in controls. The motor and sensory functions of MCAO rats with CXCR7 knockdown further decreased, and the infarct volume and cerebral edema increased. miRNA microarray data showed that seven miRNAs were differentially expressed after shRNA-CXCR7 treatment. The dual-luciferase reporter assay confirmed that miR-182 directly targeted the TCF7L2 gene. Rescue assays confirmed that TCF7L2 is downstream of CXCR7/miR-182. KEGG pathway analysis showed that the Hippo pathway may be a key pathway in CXCR7 upregulation and plays a role in protecting the brain after interventional surgery. Animal experiments have shown that CXCR7-mediated cerebral I/R injury promotes the phosphorylation of key molecules YAP and TAZ in the Hippo pathway.
Conclusion:
CXCR7 protects against cerebral I/R injury, possibly via the miR-182/TCF7L2/Hippo pathway. These results indicate that CXCR7 affects cerebral ischemia-reperfusion injury through miRNA regulation and downstream pathways.
Insights
Chemokine receptor 7 (CXCR7) protects the brain from ischemia/reperfusion injury by regulating microRNAs (miRNAs). This involves the miR-182/TCF7L2/Hippo pathway, offering new therapeutic targets for stroke.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Chemokine receptor 7 (CXCR7) has known protective effects in the brain.
- MicroRNAs (miRNAs) are implicated in cerebral ischemia/reperfusion (I/R) injury.
- The specific role of miRNAs in CXCR7-mediated brain protection remains unclear.
Purpose of the Study:
- To investigate the role of miRNAs in CXCR7-mediated brain protection following cerebral I/R injury.
- To elucidate the molecular mechanisms underlying CXCR7's protective effects in the context of stroke.
Main Methods:
- Measured CXCR7 levels in acute ischemic stroke (AIS) patients and middle cerebral artery occlusion (MCAO) rat models.
- Utilized miRNA microarray analysis to identify differentially expressed miRNAs after CXCR7 knockdown in MCAO rats.
- Performed dual-luciferase reporter assays and rescue experiments to confirm miRNA-target interactions and pathway involvement.
Main Results:
- CXCR7 expression was upregulated in MCAO rats and AIS patients.
- CXCR7 knockdown exacerbated neurological deficits, infarct volume, and cerebral edema in MCAO rats.
- miR-182 was identified as a key miRNA targeting TCF7L2, with the miR-182/TCF7L2/Hippo pathway implicated in CXCR7-mediated protection.
Conclusions:
- CXCR7 confers protection against cerebral I/R injury, potentially through the miR-182/TCF7L2/Hippo pathway.
- CXCR7 influences cerebral I/R injury via miRNA regulation and downstream signaling pathways, highlighting potential therapeutic avenues.
