Mass-spectrometry analysis of brain endothelial cells (BECs) from Foxf2iECKO and Ctrl mice

ABSTRACT: To identify the molecular and cellular pathways mediating the effects of Foxf2 in brain endothelial cells (BECs), we performed proteomic analysis of mouse BECs. For this, we applied our previously published BEC enrichment protocol using magnetic-activated cell sorting (MACS) combined with liquid chromatography-mass spectrometry (LC-MS/MS) based proteomics (Todorov-Völgyi et al., 2024) to 6 months old animals. Proteomic analysis of isolated BECs captured a total of 4750 proteins. Out of these, 320 and 434 proteins were significantly up-, and downregulated, respectively in Cdh5-CreERT2;Foxf2fl/fl (Foxf2iECKO) vs Foxf2fl/fl (Ctrl) mice. In GO enrichment analyses of significantly downregulated proteins we found ‘establishment of endothelial barrier’, ‘nitric oxide metabolic process’ and ‘positive regulation of angiogenesis’ to be among the most affected categories. Fold-change ranking of significantly altered proteins marked Tie2 as one of the most strongly downregulated proteins. Notably, several proteins involved in Tie2-regulated processes, including Nos3 and Ptgis (implicated in nitric oxide metabolic process), Rap1b, Tjp1, Cldn5, and Cdh5 (implicated in establishment of endothelial barrier), and Tie2, Eng, and Itgb1 (implicated in angiogenesis) were downregulated in BECs from Foxf2iECKO mice. Collectively, these findings demonstrate a critical role of endothelial Foxf2 in maintaining BBB integrity and Tie2 signaling.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain Microvascular Endothelial Cell, Brain Microvessel Endothelial Cell

DISEASE(S): Brain Small Vessel Disease

SUBMITTER: Stephan Mueller  

LAB HEAD: Stefan F.

PROVIDER: PXD051838 | Pride | 2025-09-02

REPOSITORIES: Pride