English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  MEG8 regulates Tissue Factor Pathway Inhibitor 2 (TFPI2) expression in the endothelium

Kremer, V., Bink I, D., Stanicek, L., van Ingen, E., Gimbel, T., Hilderink, S., et al. (2022). MEG8 regulates Tissue Factor Pathway Inhibitor 2 (TFPI2) expression in the endothelium. SCIENTIFIC REPORTS, 12(1): 843. doi:10.1038/s41598-022-04812-z.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Kremer, Veerle, Author
Bink I, Diewertje, Author
Stanicek, Laura, Author
van Ingen, Eva, Author
Gimbel, Theresa, Author
Hilderink, Sarah, Author
Guenther, Stefan1, Author              
Nossent, Anne Yael, Author
Boon, Reinier A., Author
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

Content

show
hide
Free keywords: -
 Abstract: A large portion of the genome is transcribed into non-coding RNA, which does not encode protein. Many long non-coding RNAs (lncRNAs) have been shown to be involved in important regulatory processes such as genomic imprinting and chromatin modification. The 14q32 locus contains many non-coding RNAs such as Maternally Expressed Gene 8 (MEG8). We observed an induction of this gene in ischemic heart disease. We investigated the role of MEG8 specifically in endothelial function as well as the underlying mechanism. We hypothesized that MEG8 plays an important role in cardiovascular disease via epigenetic regulation of gene expression. Experiments were performed in human umbilical vein endothelial cells (HUVECs). In vitro silencing of MEG8 resulted in impaired angiogenic sprouting. More specifically, total sprout length was reduced as was proliferation, while migration was unaffected. We performed RNA sequencing to assess changes in gene expression after loss of MEG8. The most profoundly regulated gene, Tissue Factor Pathway Inhibitor 2 (TFPI2), was fivefold increased following MEG8 silencing. TFPI2 has previously been described as an inhibitor of angiogenesis. Mechanistically, MEG8 silencing resulted in a reduction of the inhibitory histone modification H3K27me3 at the TFPI2 promoter. Interestingly, additional silencing of TFPI2 partially restored angiogenic sprouting capacity but did not affect proliferation of MEG8 silenced cells. In conclusion, silencing of MEG8 impairs endothelial function, suggesting a potential beneficial role in maintaining cell viability. Our study highlights the MEG8/TFPI2 axis as potential therapeutic approach to improve angiogenesis following ischemia.

Details

show
hide
Language(s):
 Dates: 2022-01-17
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000743649400059
DOI: 10.1038/s41598-022-04812-z
PMID: 35039572
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: SCIENTIFIC REPORTS
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 12 (1) Sequence Number: 843 Start / End Page: - Identifier: ISSN: 2045-2322