PMID- 34334113
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20220803
IS  - 1551-4005 (Electronic)
IS  - 1538-4101 (Print)
IS  - 1551-4005 (Linking)
VI  - 20
IP  - 17
DP  - 2021 Sep
TI  - ZEB2, interacting with MDM2, contributes to the dysfuntion of brain microvascular 
      endothelial cells and brain injury after intracerebral hemorrhage.
PG  - 1692-1707
LID - 10.1080/15384101.2021.1959702 [doi]
AB  - ZEB2 has been shown to be upregulated in the brain tissues of rats with 
      intracerebral hemorrhage (ICH), but its role in ICH-caused brain injury remains 
      unclear. Here, an ICH rat model was established via intracerebral injection of 
      autologous blood, and the lentivirus-mediated ZEB2 short hairpin RNA (sh-ZEB2) or 
      negative control (scramble) were administered 0.5 hours after ICH. Silencing ZEB2 
      alleviated ICH-induced neurologic deficits and the increase of BBB permeability, 
      brain water content and ZEB2 expression. Next, OGD (oxygen glucose deprivation) 
      plus hemin was used to treat primary brain microvascular endothelial cells 
      (BMECs) to simulate the ICH condition in vitro. OGD plus hemin upregulated ZEB2 
      expression and apoptosis, but reduced cell viability, migration, TEER 
      (transendothelial electric resistance) and the expression of vascular-endothelial 
      (VE-) cadherin, occludin and claudin-5, which was reversed by inhibiting ZEB2. 
      Mechanism researches showed that ZEB2 interacted with MDM2 to up-regulate MDM2 
      protein expression, and then increased E2F1 protein level by suppressing its 
      ubiquitination, which in turn promoted the transcription of ZEB2 to induce its 
      protein expression, so as to enhance the interaction between ZEB2 and MDM2, 
      thereby contributing to OGD plus hemin-induced endothelial dysfunction. 
      Additionally, the joint interference of ZEB2 and MDM2 in vivo had better 
      mitigative effects on ICH-induced brain injury compared with silencing ZEB2 
      alone. In summary, ZEB2 interacted with MDM2 to promote BMEC dysfunction and 
      brain damage after ICH.
FAU - Guo, Qingbao
AU  - Guo Q
AD  - Department of Emergency, Tangdu Hospital, The Fourth Military Medical University, 
      Xi'an, Shaanxi, China.
FAU - Xie, Manli
AU  - Xie M
AD  - Department of Occupational Diseases, Xi'an Central Hospital, Xi'an, Shaanxi, 
      China.
FAU - Guo, Miao
AU  - Guo M
AD  - Department of Pathology, Xing Yuan Hospital of Yulin, Yulin, Shaanxi, China.
FAU - Yan, Feiping
AU  - Yan F
AD  - Department of Neurosurgery, The First Hospital of Yulin, Yulin, Shaanxi, China.
FAU - Li, Lihong
AU  - Li L
AD  - Department of Emergency, Tangdu Hospital, The Fourth Military Medical University, 
      Xi'an, Shaanxi, China.
FAU - Liu, Rui
AU  - Liu R
AD  - Department of Neurosurgery, Xing Yuan Hospital of Yulin, Yulin, Shaanxi, China.
LA  - eng
PT  - Journal Article
DEP - 20210802
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Zeb2 protein, rat)
RN  - 0 (Zinc Finger E-box Binding Homeobox 2)
RN  - EC 2.3.2.27 (Mdm2 protein, rat)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/metabolism
MH  - Brain/metabolism
MH  - *Brain Injuries/etiology
MH  - Cerebral Hemorrhage/genetics
MH  - *Endothelial Cells/metabolism
MH  - Proto-Oncogene Proteins c-mdm2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Zinc Finger E-box Binding Homeobox 2
PMC - PMC8489960
OTO - NOTNLM
OT  - E2F1
OT  - Intracerebral hemorrhage
OT  - MDM2
OT  - ZEB2
OT  - brain microvascular endothelial cells
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/03 06:00
MHDA- 2022/04/08 06:00
PMCR- 2022/08/02
CRDT- 2021/08/02 05:27
PHST- 2021/08/03 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2021/08/02 05:27 [entrez]
PHST- 2022/08/02 00:00 [pmc-release]
AID - 1959702 [pii]
AID - 10.1080/15384101.2021.1959702 [doi]
PST - ppublish
SO  - Cell Cycle. 2021 Sep;20(17):1692-1707. doi: 10.1080/15384101.2021.1959702. Epub 
      2021 Aug 2.