Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway
Background: Recombinant 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 investigat...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wolters Kluwer
2017-01-01
|
Series: | Chinese Medical Journal |
Subjects: | |
Online Access: | http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=7;spage=854;epage=858;aulast=Yu |
id |
doaj-b4318c8cd72140009d1c4bd44630ba5b |
---|---|
record_format |
Article |
spelling |
doaj-b4318c8cd72140009d1c4bd44630ba5b2020-11-25T02:25:50ZengWolters KluwerChinese Medical Journal0366-69992017-01-01130785485810.4103/0366-6999.202744Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt PathwayDa-Fan YuLi-Hua ZhuLi JiangBackground: Recombinant 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. Methods: Postnatal 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. Results: In 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. Conclusions: The 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.http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=7;spage=854;epage=858;aulast=YuErythropoietin; Hypoxia-ischemia; Neovascularization; Premature Brain |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Da-Fan Yu Li-Hua Zhu Li Jiang |
spellingShingle |
Da-Fan Yu Li-Hua Zhu Li Jiang Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway Chinese Medical Journal Erythropoietin; Hypoxia-ischemia; Neovascularization; Premature Brain |
author_facet |
Da-Fan Yu Li-Hua Zhu Li Jiang |
author_sort |
Da-Fan Yu |
title |
Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway |
title_short |
Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway |
title_full |
Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway |
title_fullStr |
Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway |
title_full_unstemmed |
Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway |
title_sort |
recombinant human erythropoietin augments neovascularization responses in a neonatal rat model of premature brain damage by phosphatidylinositol 3 kinase/akt pathway |
publisher |
Wolters Kluwer |
series |
Chinese Medical Journal |
issn |
0366-6999 |
publishDate |
2017-01-01 |
description |
Background: Recombinant 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.
Methods: Postnatal 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.
Results: In 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.
Conclusions: The 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. |
topic |
Erythropoietin; Hypoxia-ischemia; Neovascularization; Premature Brain |
url |
http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=7;spage=854;epage=858;aulast=Yu |
work_keys_str_mv |
AT dafanyu recombinanthumanerythropoietinaugmentsneovascularizationresponsesinaneonatalratmodelofprematurebraindamagebyphosphatidylinositol3kinaseaktpathway AT lihuazhu recombinanthumanerythropoietinaugmentsneovascularizationresponsesinaneonatalratmodelofprematurebraindamagebyphosphatidylinositol3kinaseaktpathway AT lijiang recombinanthumanerythropoietinaugmentsneovascularizationresponsesinaneonatalratmodelofprematurebraindamagebyphosphatidylinositol3kinaseaktpathway |
_version_ |
1724850076311879680 |