Concentration-dependent duality of bFGF in regulation of barrier properties of human brain endothelial cells

Kriaučiūnaitė, Karolina; Pociūtė, Agnė; Kaušylė, Aida; Pajarskienė, Justina; Verkhratsky, Alexei; Pivoriūnas, Augustas

doi:10.1101/2021.01.07.425677

Cited by 1 publication

(2 citation statements)

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“…An example is vascular endothelial growth factor (VEGF), which loosens the barrier between endothelial cells, leading to increased vessel permeability and vascular development 8,9 . Another potent growth factor, basic fibroblast growth factor (bFGF), stabilizes the endothelial barrier at low levels, yet increases vessel permeability in a dose‐dependent manner at higher concentrations 10–14 . Lastly, sphingosine 1‐phosphate (S1P) is an abundant plasma lysosphingolipid secreted by activated platelets, 15 which greatly enhances barrier stability.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Another potent growth factor, basic fibroblast growth factor (bFGF), stabilizes the endothelial barrier at low levels, yet increases vessel permeability in a dosedependent manner at higher concentrations. [10][11][12][13][14] Lastly, sphingosine 1-phosphate (S1P) is an abundant plasma lysosphingolipid secreted by activated platelets, 15 which greatly enhances barrier stability. As plasma levels of S1P are maintained through incorporation into red blood cells and high-density lipoproteins, 16,17 endothelial cells consistently preserve a stable vascular barrier.…”

Section: Introductionmentioning

confidence: 99%

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Annexin A2 modulates phospholipid membrane composition upstream of Arp2 to control angiogenic sprout initiation

et al. 2022

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The intersection of protein and lipid biology is of growing importance for understanding how cells address structural challenges during adhesion and migration. While protein complexes engaged with the cytoskeleton play a vital role, support from the phospholipid membrane is crucial for directing localization and assembly of key protein complexes. During angiogenesis, dramatic cellular remodeling is necessary for endothelial cells to shift from a stable monolayer to invasive structures. However, the molecular dynamics between lipids and proteins during endothelial invasion are not defined. Here, we utilized cell culture, immunofluorescence, and lipidomic analyses to identify a novel role for the membrane binding protein Annexin A2 (ANXA2) in modulating the composition of specific membrane lipids necessary for cortical F‐actin organization and adherens junction stabilization. In the absence of ANXA2, there is disorganized cortical F‐actin, reduced junctional Arp2, excess sprout initiation, and ultimately failed sprout maturation. Furthermore, we observed reduced filipin III labeling of membrane cholesterol in cells with reduced ANXA2, suggesting there is an alteration in phospholipid membrane dynamics. Lipidomic analyses revealed that 42 lipid species were altered with loss of ANXA2, including an accumulation of phosphatidylcholine (16:0_16:0). We found that supplementation of phosphatidylcholine (16:0_16:0) in wild‐type endothelial cells mimicked the ANXA2 knock‐down phenotype, indicating that ANXA2 regulated the phospholipid membrane upstream of Arp2 recruitment and organization of cortical F‐actin. Altogether, these data indicate a novel role for ANXA2 in coordinating events at endothelial junctions needed to initiate sprouting and show that proper lipid modulation is a critical component of these events.

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Section: Introductionmentioning

confidence: 99%