Sortilin regulates blood-brain barrier integrity
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Sortilin regulates blood-brain barrier integrity. / Toth, Andrea E; Helms, Hans C.; Harazin, Andras; Johnsen, Kasper B; Goldeman, Charlotte; Burkhart, Annette; Thomsen, Maj S; Kempen, Paul J; Klepe, Adrian; Lipka, Dora V; Møller, Peter L.; Andresen, Thomas L.; Nyegaard, Mette; Moos, Torben; Brodin, Birger; Nielsen, Morten S.
In: The FEBS Journal, Vol. 289, No. 4, 2022, p. 1062-1079.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Sortilin regulates blood-brain barrier integrity
AU - Toth, Andrea E
AU - Helms, Hans C.
AU - Harazin, Andras
AU - Johnsen, Kasper B
AU - Goldeman, Charlotte
AU - Burkhart, Annette
AU - Thomsen, Maj S
AU - Kempen, Paul J
AU - Klepe, Adrian
AU - Lipka, Dora V
AU - Møller, Peter L.
AU - Andresen, Thomas L.
AU - Nyegaard, Mette
AU - Moos, Torben
AU - Brodin, Birger
AU - Nielsen, Morten S
N1 - This article is protected by copyright. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Brain homeostasis depends on the existence of the blood-brain barrier (BBB). Despite decades of research, the factors and signalling pathways for modulating and maintaining BBB integrity are not fully elucidated. Here, we characterize the expression and function of the multifunctional receptor, sortilin, in the cells of the BBB, in vivo and in vitro. We show that sortilin acts as an important regulatory protein of the BBB's tightness. In rats lacking sortilin, the BBB was leaky, which correlated well with relocated distribution of the localisation of zonula occludens-1, VE-cadherin and β-catenin junctional proteins. Furthermore, the absence of sortilin in brain endothelial cells resulted in decreased phosphorylation of Akt signalling protein and increased the level of phospho-ERK1/2. As a putative result of MAPK/ERK pathways activity, the junctions between the brain endothelial cells were disintegrated and the integrity of the BBB became compromised. The identified barrier differences between wild type and Sort1-/- brain endothelial cells can pave the way for a better understanding of sortilin's role in the healthy and diseased BBB.
AB - Brain homeostasis depends on the existence of the blood-brain barrier (BBB). Despite decades of research, the factors and signalling pathways for modulating and maintaining BBB integrity are not fully elucidated. Here, we characterize the expression and function of the multifunctional receptor, sortilin, in the cells of the BBB, in vivo and in vitro. We show that sortilin acts as an important regulatory protein of the BBB's tightness. In rats lacking sortilin, the BBB was leaky, which correlated well with relocated distribution of the localisation of zonula occludens-1, VE-cadherin and β-catenin junctional proteins. Furthermore, the absence of sortilin in brain endothelial cells resulted in decreased phosphorylation of Akt signalling protein and increased the level of phospho-ERK1/2. As a putative result of MAPK/ERK pathways activity, the junctions between the brain endothelial cells were disintegrated and the integrity of the BBB became compromised. The identified barrier differences between wild type and Sort1-/- brain endothelial cells can pave the way for a better understanding of sortilin's role in the healthy and diseased BBB.
U2 - 10.1111/febs.16225
DO - 10.1111/febs.16225
M3 - Journal article
C2 - 34626084
VL - 289
SP - 1062
EP - 1079
JO - F E B S Journal
JF - F E B S Journal
SN - 1742-464X
IS - 4
ER -
ID: 281945194