Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway.
- Author:
Da-Fan YU
1
;
Li-Hua ZHU
2
;
Li JIANG
2
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Animals, Newborn; Antigens, CD34; metabolism; Brain; drug effects; metabolism; pathology; Disease Models, Animal; Erythropoietin; genetics; metabolism; therapeutic use; Female; Humans; Hypoxia-Ischemia, Brain; drug therapy; metabolism; Neovascularization, Physiologic; drug effects; Phosphatidylinositol 3-Kinase; metabolism; Pregnancy; Proto-Oncogene Proteins c-akt; metabolism; Rats; Rats, Sprague-Dawley; Recombinant Proteins; genetics; metabolism; therapeutic use; Signal Transduction; drug effects; Vascular Endothelial Growth Factor A; genetics; Vascular Endothelial Growth Factor Receptor-2; metabolism
- From: Chinese Medical Journal 2017;130(7):854-858
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDRecombinant human-erythropoietin (rh-EPO) has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation. In the present study, we found that the rh-EPO was related to the promotion of neovascularization. Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway.
METHODSPostnatal day 5 (PD5), rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h. All the rat pups were randomized into five groups as follows: (1) control group; (2) hypoxia-ischemic (HI) group; (3) HI + LY294002 group; (4) HI + rh-EPO group; and (5) HI + rh-EPO + LY294002 group. The phospho-Akt protein was tested 90 min after the whole operation, and CD34, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor (VEGF) were also tested 2 days after the whole operation.
RESULTSIn the hypoxic and ischemic zone of the premature rat brain, the rh-EPO induced CD34+ cells to immigrate to the HI brain zone (P < 0.05) and also upregulated the VEGFR2 protein expression (P < 0.05) and VEGF mRNA level (P < 0.05) through the PI3K/Akt (P < 0.05) signaling pathway when compared with other groups.
CONCLUSIONSThe rh-EPO treatment augments neovascularization responses in the neonatal rat model of premature brain damage through the PI3K/Akt signaling pathway. Besides, the endogenous EPO may exist in the HI zone of rat brain and also has neovascularization function through the PI3K/Akt signaling pathway.
