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Peptide5 Attenuates rtPA Related Brain Microvascular Endothelial Cells Reperfusion Injury via the Wnt/β-Catenin Signalling Pathway
- Source :
- Current Neurovascular Research. 18:219-226
- Publication Year :
- 2021
- Publisher :
- Bentham Science Publishers Ltd., 2021.
-
Abstract
- Aims: Brain vascular endothelial cell dysfunction after rtPA treatment is a significant factor associated with poor prognosis, suggesting that alleviation of rtPA-related endothelial cell injury may represent a potential beneficial strategy along with rtPA thrombolysis. Background: Thrombolysis with recombinant tissue plasminogen activator (rtPA) is beneficial for acute ischemic stroke but may increase the risk of Hemorrhagic Transformation (HT), which is considered ischemia-reperfusion injury. The underlying reason may contribute to brain endothelial injury and dysfunction related to rtPA against ischemic stroke. As previous studies have demonstrated that transiently blocked Cx43 using peptide5 (Cx43 mimetic peptide) during retinal ischemia reduced vascular leakage, it is necessary to know whether this might help decrease side effect of rtPA within the therapeutic time window. Objective: In this study, we established a cell hypoxia/reoxygenation H/R model in cultured primary Rat Brain Microvascular Endothelial Cells (RBMECs) and evaluated endothelial cell death and permeability after rtPA treatment with or without transient peptide5. In addition, we also investigated the potential signaling pathway to explore the underlying mechanisms preliminarily. Results: The results showed that peptide5 inhibited rtPA-related endothelial cell death and permeability. It also slightly increased tight junction (ZO-1, occluding, claudin-5) and β-catenin mRNA expression, demonstrating that peptide5 might attenuate endothelial cell injury by regulating the Wnt/ β-catenin pathway. The following bioinformatic exploration from the GEO dataset GSE37239 was also consistent with our findings. Methods: In this study, we established a cell hypoxia/reoxygenation H/R model in cultured primary Rat Brain Microvascular Endothelial Cells (RBMECs) and evaluated endothelial cell death and permeability after rtPA treatment with or without transient peptide5. In addition, we also investigated the potential signaling pathway to explore the underlying mechanisms preliminarily. Results: The results showed that peptide5 inhibited rtPA-related endothelial cell death and permeability. It also slightly increased tight junction (ZO-1, occluding, claudin-5) and β-catenin mRNA expression, demonstrating that peptide5 might attenuate endothelial cell injury by regulating the Wnt/ β-catenin pathway. The following bioinformatic exploration from the GEO dataset GSE37239 was also consistent with our findings. Conclusion: This study showed that the application of peptide5 maintained cell viability and permeability associated with rtPA treatment, revealing a possible pathway that could be exploited to limit rtPA-related endothelial cell injury during ischemic stroke. Furthermore, the altered Wnt/β- catenin signaling pathway demonstrated that signaling pathways associated with Cx43 might have potential applications in the future. This study may provide a new way to attenuate HT and assist the application of rtPA in ischemic stroke.
- Subjects :
- Side effect
Brain Ischemia
Rats, Sprague-Dawley
Cellular and Molecular Neuroscience
Developmental Neuroscience
medicine
Animals
Viability assay
Wnt Signaling Pathway
business.industry
Wnt signaling pathway
Brain
Endothelial Cells
Hypoxia (medical)
medicine.disease
Hedgehog signaling pathway
Rats
Endothelial stem cell
Neurology
Connexin 43
Reperfusion Injury
Tissue Plasminogen Activator
Cancer research
medicine.symptom
Signal transduction
business
Reperfusion injury
Subjects
Details
- ISSN :
- 15672026
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Current Neurovascular Research
- Accession number :
- edsair.doi.dedup.....eee2425f53576792d30285ca13c8efec