Transcriptomics

Dataset Information

0

Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation


ABSTRACT: TDP-43 is a DNA/RNA-binding protein that regulates gene expression and its malfunction in neurons has been causally associated with multiple neurodegenerative disorders. Although progress has been made in understanding the functions of TDP-43 in neurons, little is known about its role in endothelial cells (ECs), angiogenesis and vascular function. Using inducible EC-specific TDP-43 knockout mice, we show that TDP-43 is required for sprouting angiogenesis, vascular barrier integrity and blood vessel stability. Postnatal EC-specific deletion of TDP-43 leads to retinal hypovascularization due to defects in vessel sprouting associated with reduced EC proliferation and migration. In mature blood vessels, loss of TDP-43 disrupts the blood-brain barrier and triggers vascular degeneration. These vascular defects are associated with an inflammatory response in the central-nervous system with activation of microglia and astrocytes. Mechanistically, deletion of TDP-43 disrupts fibronectin matrix around sprouting vessels and reduces -catenin signaling in ECs. Together, our results indicate that TDP-43 is essential for the formation of a stable and mature vasculature.

ORGANISM(S): Mus musculus

PROVIDER: GSE253868 | GEO | 2024/02/01

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2016-11-17 | E-MTAB-4842 | biostudies-arrayexpress
2021-09-30 | GSE161310 | GEO
2021-09-30 | GSE161236 | GEO
2005-12-20 | E-GEOD-3874 | biostudies-arrayexpress
2020-02-13 | E-MTAB-8077 | biostudies-arrayexpress
2023-02-23 | MSV000091355 | MassIVE
2024-07-25 | PXD045899 | Pride
2015-01-28 | PXD001186 | Pride
2019-04-11 | PXD013192 | Pride
2005-12-21 | GSE3874 | GEO