PMID- 34551201
OWN - NLM
STAT- MEDLINE
DCOM- 20220321
LR  - 20220321
IS  - 1932-7005 (Electronic)
IS  - 1932-6254 (Linking)
VI  - 15
IP  - 12
DP  - 2021 Dec
TI  - Brain endothelial cells-derived extracellular vesicles overexpressing ECRG4 
      inhibit glioma proliferation through suppressing inflammation and angiogenesis.
PG  - 1162-1171
LID - 10.1002/term.3244 [doi]
AB  - Esophageal cancer related gene-4 (ECRG4) has been shown to be a candidate tumor 
      suppressor in many tumors, but its role in glioma remains poorly understood. This 
      study aimed to explore whether extracellular vesicles (EVs) derived from brain 
      endothelial cells which overexpressed ECRG4 have anti-tumor effect on gliomas in 
      vivo and in vitro, as well as the possible mechanism. A constructed lentivirus 
      expressing the ECRG4 gene was transfected into the hCMEC/D3 cell line. The EVs 
      were isolated from the cells and characterized by Western blot with exosome 
      markers of CD9, CD63, CD81, Alix. RT-PCR and Western blot were performed to 
      verify ECRG4 expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium 
      bromide and clone formation assays were applied to detect the proliferation of 
      glioma cells incubated with EVs expressing the ECRG4 (ECRG4-exo). The level of 
      inflammatory cytokines and angiogenesis related factors, including nuclear factor 
      kappa-B (NF-kappaB), interleukin (IL)-1beta, IL-6, IL-8, monocyte chemoattractant 
      protein-1 (MCP-1), hypoxia-inducible factor 1-alpha (HIF-1alpha), vascular 
      endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 
      2 (VEGFR2) levels were detected by ELISA. The T98G cell xenograft mouse model was 
      established and treated with ECRG4-EV. The tumor volume and weight were recorded. 
      p38-MAPK, p-p38-MAPK proteins were determined by Western blot in tumor tissues. 
      As a result, EVs can be internalized into U87MG and T98G cells. ECRG4-EV 
      inhibited U87MG and T98G cell proliferation. ECRG4-EV also inhibited the 
      expression of factors involved in inflammation and angiogenesis. In addition, 
      ECRG4-EVs suppressed tumor growth and decreased the production of inflammatory 
      cytokines through inactivation of p38-MAPK signal pathway. In conclusion, 
      ECRG4-EVsuppresses glioma proliferation through modulating the inflammation and 
      angiogenesis.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Huo, Haoran
AU  - Huo H
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Yang, Song
AU  - Yang S
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Wu, Haotian
AU  - Wu H
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Sun, Yuchen
AU  - Sun Y
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Zhao, Ranran
AU  - Zhao R
AD  - Department of Hemodialysis, Traditional Chinese Medicine Hospital of Shi Jia 
      Zhuang City, Shijiazhuang, Hebei, China.
FAU - Ye, Ruihao
AU  - Ye R
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Yan, Dongdong
AU  - Yan D
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Shi, Xuefang
AU  - Shi X
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Yang, Jiankai
AU  - Yang J
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
LA  - eng
GR  - 21377751D/S&T Program of Hebei/
GR  - 19JCZDJC65300(Z)/Beijing-Tianjin-Hebei Province Basic Research Cooperation 
      Project/
GR  - F2019206706/Beijing-Tianjin-Hebei Province Basic Research Cooperation Project/
GR  - A202103004/Hebei high level Talents Project/
GR  - 2020TXJC08/the Hebei Medical University-Hebei Provincial Science and Technology 
      Department Innovation Fund/
GR  - Provincial Clinical Medical Talents Project in 2021/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210929
PL  - England
TA  - J Tissue Eng Regen Med
JT  - Journal of tissue engineering and regenerative medicine
JID - 101308490
RN  - 0 (ECRG4 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Brain
MH  - Cell Line, Tumor
MH  - *Cell Proliferation
MH  - Endothelial Cells/*metabolism/pathology
MH  - Extracellular Vesicles/genetics/*metabolism/pathology
MH  - Glioma/genetics/*metabolism/pathology
MH  - Humans
MH  - Neovascularization, Pathologic/genetics/*metabolism/pathology
MH  - Tumor Suppressor Proteins/genetics/*metabolism
OTO - NOTNLM
OT  - ECRG4
OT  - exosome
OT  - glioma
OT  - inflammatory factors
OT  - p38-MAPK
EDAT- 2021/09/23 06:00
MHDA- 2022/03/22 06:00
CRDT- 2021/09/22 17:35
PHST- 2021/08/22 00:00 [revised]
PHST- 2021/05/27 00:00 [received]
PHST- 2021/09/02 00:00 [accepted]
PHST- 2021/09/23 06:00 [pubmed]
PHST- 2022/03/22 06:00 [medline]
PHST- 2021/09/22 17:35 [entrez]
AID - 10.1002/term.3244 [doi]
PST - ppublish
SO  - J Tissue Eng Regen Med. 2021 Dec;15(12):1162-1171. doi: 10.1002/term.3244. Epub 
      2021 Sep 29.