PMID- 35754359
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20230701
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 42
IP  - 11
DP  - 2022 Nov
TI  - RNF213 loss of function reshapes vascular transcriptome and spliceosome leading 
      to disrupted angiogenesis and aggravated vascular inflammatory responses.
PG  - 2107-2122
LID - 10.1177/0271678X221110679 [doi]
AB  - RNF213 gene mutations are the cause behind Moyamoya disease, a rare 
      cerebrovascular occlusive disease. However, the function of RNF213 in the 
      vascular system and the impact of its loss of function are not yet comprehended. 
      To understand RNF23 function, we performed gene knockdown (KD) in vascular cells 
      and performed various phenotypical analysis as well as extensive transcriptome 
      and epitranscriptome profiling. Our data revealed that RNF213 KD led to disrupted 
      angiogenesis in HUVEC, in part due to downregulation of DNA replication and 
      proliferation pathways. Furthermore, HUVEC cells became sensitive to LPS induced 
      inflammation after RNF213 KD, leading to retarded cell migration and enhanced 
      macrophage transmigration. This was evident at the level of transcriptome as 
      well. Interestingly, RNF213 led to extensive changes in mRNA splicing that were 
      not previously reported. In vascular smooth muscle cells (vSMCs), RNF213 KD led 
      to alteration in cytoskeletal organization, contractility, and vSMCs function 
      related pathways. Finally, RNF213 KD disrupted endothelial-to-vSMCs communication 
      in co-culture models. Overall, our results indicate that RNF213 KD sensitizes 
      endothelial cells to inflammation, leading to altered angiogenesis. Our results 
      shed the light on the important links between RNF213 mutations and 
      inflammatory/immune inducers of MMD and on the unexplored role of 
      epitranscriptome in MMD.
FAU - Zhang, Liyin
AU  - Zhang L
AD  - Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku 
      University Graduate School of Medicine, Sendai, Japan.
FAU - Rashad, Sherif
AU  - Rashad S
AUID- ORCID: 0000-0002-4511-6360
AD  - Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku 
      University Graduate School of Medicine, Sendai, Japan.
AD  - Department of Neurosurgical Engineering and Translational Neuroscience, Graduate 
      School of Biomedical Engineering, Tohoku University, Sendai, Japan.
AD  - Department of Neurosurgery, Tohoku University Graduate School of Medicine, 
      Sendai, Japan.
FAU - Zhou, Yuan
AU  - Zhou Y
AD  - Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku 
      University Graduate School of Medicine, Sendai, Japan.
FAU - Niizuma, Kuniyasu
AU  - Niizuma K
AUID- ORCID: 0000-0001-9282-6499
AD  - Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku 
      University Graduate School of Medicine, Sendai, Japan.
AD  - Department of Neurosurgical Engineering and Translational Neuroscience, Graduate 
      School of Biomedical Engineering, Tohoku University, Sendai, Japan.
AD  - Department of Neurosurgery, Tohoku University Graduate School of Medicine, 
      Sendai, Japan.
FAU - Tominaga, Teiji
AU  - Tominaga T
AD  - Department of Neurosurgery, Tohoku University Graduate School of Medicine, 
      Sendai, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220625
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.2.27 (RNF213 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
SB  - IM
MH  - Adenosine Triphosphatases/genetics
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Humans
MH  - Inflammation/genetics
MH  - Lipopolysaccharides
MH  - *Moyamoya Disease
MH  - Neovascularization, Pathologic/genetics
MH  - RNA, Messenger
MH  - Spliceosomes/metabolism
MH  - Transcription Factors
MH  - *Transcriptome
MH  - Ubiquitin-Protein Ligases/genetics/metabolism
PMC - PMC9580177
OTO - NOTNLM
OT  - Moyamoya
OT  - RNF213
OT  - alternative splicing
OT  - angiogenesis
OT  - endothelial cells
OT  - epitranscriptome
COIS- The author(s) declared no potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article.
EDAT- 2022/06/28 06:00
MHDA- 2022/10/19 06:00
PMCR- 2023/06/25
CRDT- 2022/06/27 03:14
PHST- 2022/06/28 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/06/27 03:14 [entrez]
PHST- 2023/06/25 00:00 [pmc-release]
AID - 10.1177_0271678X221110679 [pii]
AID - 10.1177/0271678X221110679 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2022 Nov;42(11):2107-2122. doi: 
      10.1177/0271678X221110679. Epub 2022 Jun 25.