EPCs-derived conditioned medium mitigates chronic cerebral ischemic injury through the MIF-activated AKT pathway
Cheng, Y.-W.; Yang, L.-Y.; Chen, Y.-T.; Chou, S. C.; Chen, K.-W.; Chen, Y.-H.; Deng, C.-R.; Chen, I.-C.; Chou, W.-J.; Chang, C.-C.; Chen, Y.-R.; Hwa, H.-L.; Wang, K.-C.; Kuo, M.-F.
Show abstract
BackgroundChronic cerebral ischemia (CCI) is considered as a prelude to neurodegeneration. Endothelial progenitor cells (EPCs) have been implicated in revascularization and vascular repair in cerebral ischemic diseases. Due to the safety concern and the low survival rate of the transplanted cells, interest has shifted toward the paracrine effect of EPCs. Here, we investigate the effects of EPC-derived conditioned medium (EPC-CM) on the vascular and functional impairments in a rodent model of CCI and the mechanism via which the EPC-CM involves. MethodsBilateral internal carotid artery ligation (BICAL) was performed in rats to induce cerebral ischemia. EPC-CM was intracisternally injected 1 week after BICAL. The changes of the microvasculature and behavior were examined 3 weeks after BICAL. The EPC-CM was analyzed by cytokine array for the factors that involved in angiogenesis. The therapeutic effects and mechanism of the candidate factor was validated with oxygen-glucose deprivation-injured endothelial cells and EPCs in vitro. ResultsEPC-CM significantly improved the vascular, motor and cognitive impairments of the BICAL rats. Macrophage migration inhibitory factor (MIF) was identified as a key factor in EPC-CM involved in angiogenesis and anti-senescence. Furthermore, recombinant MIF protein mirrored the effects of EPC-CM on EPCs and ECs. These therapeutic effects were decreased by the co-treatment with EPC-CM and MIF-specific antibody both in vivo and in vitro. MIF operates through multiple pathways, including the AKT pathway, which plays a crucial role in cellular homeostasis. Inhibiting the AKT pathway diminished the protective effect of MIF in the CCI model. ConclusionsWe demonstrated that EPC-CM protected the chronic ischemic rat brain from ischemic injury and promoted functional recovery in rats through MIF-mediated AKT pathway, which indicated that EPC-CM may serve as an alternative potential therapy in chronic cerebral ischemia.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Age-stratified Prevalence and Relative Prognostic Significance of Traditional Atherosclerotic Risk Factors: A Report from the Nationwide Registry of Percutaneous Coronary Interventions in Japan 93%
- Deviation From Personalized Blood Pressure Targets Correlates With Worse Outcome After Successful Recanalization 92%
- Predictors of survival in patients with ischemic stroke and active cancer: A prospective, multicenter, observational study 92%
Similar papers in this journal
- Metformin prevented high glucose-induced endothelial reactive oxygen species via OGG1 in an AMPKα-Lin-28 dependent pathway 95%
- Ginsenoside Rg1 defenses PC-12 cells against hydrogen peroxide-caused damage via up-regulation of miR-216a-5p 92%
- KHDRBS3 facilitates self-renewal and temozolomide resistance of glioblastoma cell lines 91%
Similar papers in this journal
- Enhancing NADPH to Restore Redox Homeostasis and Lysosomal Function in G6PD-Deficient Microglia 92%
- The defects of the hippocampal ripples and theta rhythm in depression, and the effects of physical exercise on their amelioration. 90%
- Glabridin induces paraptosis-like cell death via ER stress in breast cancer cells 90%
Similar papers in this journal
- Neuroprotection in early stages of Alzheimers Disease is promoted by Transthyretin angiogenic properties 92%
- A Human Neuron Alzheimer's Disease Model Reveals Barriers to Senolytic Translatability 89%
- p75 Neurotrophin Receptor Shapes the Dynamics of Adult Hippocampal Neurogenesis in Alzheimer's Disease 88%
Similar papers in this journal
- MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat 96%
- Multi-omics-based analysis of the effect of longevity genes on the immune relevance of colorectal cancer 92%
- A prognostic model for Senescence-related LncRNA in a novel colon adenocarcinoma based on WGCNA and LASSO regression 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.