Transcriptomics

Dataset Information

0

Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases


ABSTRACT: Endothelial cells control inflammation in inflammatory and infectious diseases through regulating endothelial gene expression and permeability. Roundabout4 (Robo4) is an endothelial-specific protein that stabilizes endothelial cells. Robo4 has been shown to ameliorate mouse inflammatory and severe infectious diseases, such as sepsis and COVID-19 by reducing vascular permeability. Despite this, it remains uncertain whether these are the only mechanisms by which Robo4 ameliorates the diseases. In this study, we carried out an RNA-seq analysis to investigate the genes regulated by Robo4 in endothelial cells stimulated by TNFα and identified gene, prostaglandin-endoperoxide synthase 2 (PTGS2) , which codes for Cycloocygenase-2 (COX-2). Mechanistic analysis revealed that Robo4 curbs COX-2 expression and endothelial hyperpermeability by preventing prolonged Rac1 activation. Analysis of Robo4 interacting protein identified IQ motif containing GTPase activating protein 1 (IQGAP1) that maintains active Rac1. Robo4 enhanced ubiquitination of IQGAP1 with a ubiquitin E3 ligase, TNF receptor-associated factor 7 (TRAF7), to inactivate Rac1. Finally, Robo4 deficiency exacerbates COX-2 -associated inflammatory diseases, including arthritis, edema, and pain in mouse models. Taken together, Robo4 inhibits Rac1 activation by interacting with TRAF7 and IQGAP1, thereby suppressing the endothelial expression of COX-2 and reducing hyperpermeability. Thus, we uncovered further Robo4 capabilities that suppresses COX-2 and inflammatory diseases, as well as their underlying mechanisms, indicating that endothelial Robo4 is a potential therapeutic target for diverse inflammatory diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE231460 | GEO | 2024/05/16

REPOSITORIES: GEO

Dataset's files

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

Similar Datasets

| PRJNA966093 | ENA
2023-01-15 | GSE165000 | GEO
2016-11-28 | GSE58663 | GEO
2023-06-01 | GSE229698 | GEO
| PRJNA253123 | ENA
2016-08-14 | E-GEOD-84345 | biostudies-arrayexpress
2024-01-01 | GSE238019 | GEO
2018-05-21 | GSE45540 | GEO
2018-05-21 | GSE45539 | GEO
| PRJNA488555 | ENA