Role of Nuclear-Receptor-Related 1 in the Synergistic Neuroprotective Effect of Umbilical Cord Blood and Erythropoietin Combination Therapy in Hypoxic Ischemic Encephalopathy

• Published in: International journal of molecular sciences 2022-03, Vol.23 (5), p.2900
• Main Authors: Choi, Joo-Wan, Kang, Su Jung, Choi, Jee In, Kwack, KyuBum, Kim, MinYoung
• Format: Article
• Language: English
• Subjects: Animals; beta Catenin; Blood; Brain damage; Brain research; Cerebral palsy; Combination therapy; comprehensive analysis; Cord blood; Disability; Disease Models, Animal; Dopamine; Encephalopathy; Epoetin Alfa - therapeutic use; Erythropoietin; Erythropoietin - genetics; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Experiments; Fetal Blood; Gene expression; Genomes; human cord blood cell therapy; Hypoxia; Hypoxia-Ischemia, Brain - drug therapy; hypoxic-ischemic brain injury; Ischemia; Mice; microarray; Neonates; Neurogenesis; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Nuclear receptors; Nurr1 protein; Receptors, Cytoplasmic and Nuclear; Recombinant Proteins - therapeutic use; Synergistic effect; Transcriptomics; Umbilical cord; Wnt protein; β-Catenin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23052900

Neonatal hypoxic-ischemic encephalopathy (HIE) results in neurological impairments; cell-based therapy has been suggested as a therapeutic avenue. Previous research has demonstrated the synergistically potentiated therapeutic efficacy of human umbilical cord blood (UCB) by combining recombinant human erythropoietin (EPO) treatment for recovery from HIE. However, its molecular mechanism is not entirely understood. In the present study, we analyzed the mechanisms underlying the effect of combination treatment with EPO and UCB by transcriptomic analysis, followed by gene enrichment analysis. Mouse HIE model of the neonate was prepared and randomly divided into five groups: sham, HIE, and UCB, EPO, and UCB+EPO treatments after HIE. A total of 376 genes were differentially expressed when |log2FC| ≥ 1-fold change expression values were considered to be differentially expressed between UCB+EPO and HIE. Further assessment through qRT-PCR and gene enrichment analysis confirmed the expression and correlation of its potential target, , as an essential gene involved in the synergistic effect of the UCB+EPO combination. The results indicated the remarkable activation of Wnt/β-catenin signaling by reducing the infarct size by UCB+EPO treatment, accompanied by activity. In conclusion, these findings suggest that the regulation of Nurr1 through the Wnt/β-catenin pathway exerts a synergistic neuroprotective effect in UCB and EPO combination treatment.