PMID- 30565676
OWN - NLM
STAT- MEDLINE
DCOM- 20200408
LR  - 20200408
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 234
IP  - 6
DP  - 2019 Jun
TI  - Roles of Nrf2/HO-1 and HIF-1alpha/VEGF in lung tissue injury and repair following 
      cerebral ischemia/reperfusion injury.
PG  - 7695-7707
LID - 10.1002/jcp.27767 [doi]
AB  - Cerebral ischemia/reperfusion injury (CIRI) leads to injury in distant organs, 
      most commonly the lungs, although limited studies have examined self-protective 
      mechanisms during CIRI-induced lung injury. Here, we investigated self-protective 
      mechanisms that attenuate stress-related injury and promote the angiogenetic 
      repair of epithelial function during CIRI-induced lung injury by measuring 
      nuclear factor erythroid-related factor 2 (Nrf2) and hypoxia-inducible factor-1alpha 
      (HIF-1alpha) levels. A CIRI model was established in male Sprague-Dawley rats by 
      blocking the middle cerebral artery. Rats were divided into five subgroups based 
      on the reperfusion time (6, 12, 24, 48, and 72 hr). Lung injury was assessed 
      using a semiquantitative score and a thiobarbituric acid-based method of 
      determining malonaldehyde production. Lung tissue angiogenesis was detected by 
      CD34 and CD31 immunolabeling. Changes in Nrf2, heme oxygenase-1 (HO-1), HIF-1alpha, 
      vascular-endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), 
      extracellular-regulated kinase1/2 (ERK1/2), and phospho-ERK1/2 ( p-ERK1/2) 
      protein- and mRNA-expression levels were measured by immunohistochemistry and 
      reverse transcription polymerase chain reactions, respectively. Oxidative stress 
      induced by cerebral ischemia/reperfusion (CI/R) caused lung injury. Expression of 
      the Nrf2/HO-1 antioxidative stress pathway in lung tissues increased following 
      CI/R, peaking after 24 hr. PI3K, ERK, and p-ERK1/2, which act upstream of 
      Nrf2/HO-1, were expressed at higher levels in the CI/R-model group, consistent 
      with the general trends observed for Nrf2/HO-1. Within 72 hr post-CI/R, HIF-1alpha, 
      and VEGF expression significantly increased versus the sham group. Thus, during 
      CIRI-induced lung injury, the body may upregulate antioxidative stress activities 
      and promote angiogenesis to repair the endothelial barrier through the Nrf2/HO-1 
      and HIF-1alpha/VEGF signaling pathways, enabling self-protection.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Fan, Jianhua
AU  - Fan J
AD  - Department of Neurology, The Fourth Affiliated Hospital of China Medical 
      University, Shenyang, Liaoning, China.
FAU - Lv, Hui
AU  - Lv H
AD  - Department of Neurology, The Fourth Affiliated Hospital of China Medical 
      University, Shenyang, Liaoning, China.
FAU - Li, Jie
AU  - Li J
AD  - Department of Neurology, The Fourth Affiliated Hospital of China Medical 
      University, Shenyang, Liaoning, China.
FAU - Che, Yuqin
AU  - Che Y
AD  - Department of Neurology, The Fourth Affiliated Hospital of China Medical 
      University, Shenyang, Liaoning, China.
FAU - Xu, Baoning
AU  - Xu B
AD  - Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical 
      University, Shenyang, Liaoning, China.
FAU - Tao, Zuo
AU  - Tao Z
AD  - Department of China Medical University, Shenyang, China.
FAU - Jiang, Wenjun
AU  - Jiang W
AUID- ORCID: 0000-0002-8880-2117
AD  - Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical 
      University, Shenyang, Liaoning, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181122
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/complications/metabolism
MH  - Heme Oxygenase-1/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Lung/metabolism
MH  - Lung Injury/*metabolism
MH  - Male
MH  - NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress/physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*metabolism
MH  - Vascular Endothelial Growth Factor A/*metabolism
OTO - NOTNLM
OT  - acute lung injury
OT  - angiogenesis
OT  - antioxidative stress
OT  - cerebral ischemia/reperfusion injury
OT  - nuclear factor erythroid-related factor 2
EDAT- 2018/12/20 06:00
MHDA- 2020/04/09 06:00
CRDT- 2018/12/20 06:00
PHST- 2018/05/10 00:00 [received]
PHST- 2018/10/30 00:00 [accepted]
PHST- 2018/12/20 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2018/12/20 06:00 [entrez]
AID - 10.1002/jcp.27767 [doi]
PST - ppublish
SO  - J Cell Physiol. 2019 Jun;234(6):7695-7707. doi: 10.1002/jcp.27767. Epub 2018 Nov 
      22.