Protective effect of conditioned medium from brain pericytes overexpressing telomerase reverse transcriptase on hypoxic-ischemic neurons

Abstract

Abstract Aims: Cerebral microvascular pericytes can secrete both neurotrophic factors and neurotoxic molecules, which together construct the microenvironment for nerve growth and repair. The aim of this study is to detect the effect of telomerase reverse transcriptase (TERT) overexpression on the change of secretory spectrum of brain pericytes, and to examine the protective effect and mechanism of conditioned medium from brain pericytes overexpressing TERTon hypoxic-ischemic neurons. Methods:TERT overexpressing pericytes were constructedand the conditioned medium was collected. Cortical neurons weresubjected to oxygen-glucose deprivation (OGD) and cultured in neurobasal/B27 or conditioned medium from pericytes, andtheir survival and apoptosis were detected.Furthermore, conditioned medium was analyzed using Tandem Mass Tagstechnology to examine the differentially expressed proteins. Then these proteins were analyzedand the key proteins related to neuronal protectionwere selected and verified. Results: Conditioned medium from pericytes increased survival and decreased apoptosis of OGD neurons, and TERT over-expression enhanced this effect. The quantitative proteomics of conditioned mediumselected 12 differentially expressedproteins which were related to neuronal protection, among them FGF2 and apoE4 were determined as the possible effectors to regulate neuronal survival inconditioned medium from brain pericytes overexpressing TERT through verification experiments. Mechanistically, TERT regulated the expression of FGF2 and ApoE4 through activating Akt signaling. Conclusion: TERT overexpression enhanced the neuroprotective effect of conditioned mediumthrough improving the secretion profile of pericytes. Conditioned medium from brain pericytes overexpressing TERT has the potential to be developed as an effective neuroprotective agent.