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Blockade of 67-kDa Laminin Receptor Facilitates AQP4 Down-Regulation and BBB Disruption via ERK1/2-and p38 MAPK-Mediated PI3K/AKT Activations

by 1,2, 1,2, 1,2 and 1,2,*
1
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, Korea
2
Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, Korea
*
Author to whom correspondence should be addressed.
Cells 2020, 9(7), 1670; https://doi.org/10.3390/cells9071670
Received: 2 June 2020 / Revised: 9 July 2020 / Accepted: 10 July 2020 / Published: 11 July 2020
(This article belongs to the Special Issue Advances in Aquaporins)
Recently, we have reported that dysfunctions of 67-kDa laminin receptor (67LR) induced by status epilepticus (SE, a prolonged seizure activity) and 67LR neutralization are involved in vasogenic edema formation, accompanied by the reduced aquaporin 4 (AQP4, an astroglial specific water channel) expression in the rat piriform cortex (PC). In the present study, we found that the blockade of 67LR activated p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways, which enhanced phosphatidylinositol 3 kinase (PI3K)/AKT phosphorylations in endothelial cells and astrocytes, respectively. 67LR-p38 MAPK-PI3K-AKT activation in endothelial cells increased vascular permeability. In contrast, 67LR-ERK1/2-PI3K-AKT signaling pathways in astrocytes regulated astroglial viability and AQP4 expression. These findings indicate that PI3K/AKT may integrate p38 MAPK and ERK1/2 signaling pathways to regulate AQP4 expression when 67LR functionality is reduced. Thus, we suggest that 67LR-p38 MAPK/ERK1/2-PI3K-AKT-AQP4 signaling cascades may mediate serum extravasation and AQP4 expression in astroglio-vascular systems, which is one of the considerable therapeutic targets for vasogenic edema in various neurological diseases. View Full-Text
Keywords: 3CAI; astrocyte; endothelial cell; piriform cortex; SB202190; SMI-71; U0126; wortmannin 3CAI; astrocyte; endothelial cell; piriform cortex; SB202190; SMI-71; U0126; wortmannin
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MDPI and ACS Style

Kim, J.-E.; Park, H.; Lee, J.-E.; Kang, T.-C. Blockade of 67-kDa Laminin Receptor Facilitates AQP4 Down-Regulation and BBB Disruption via ERK1/2-and p38 MAPK-Mediated PI3K/AKT Activations. Cells 2020, 9, 1670. https://doi.org/10.3390/cells9071670

AMA Style

Kim J-E, Park H, Lee J-E, Kang T-C. Blockade of 67-kDa Laminin Receptor Facilitates AQP4 Down-Regulation and BBB Disruption via ERK1/2-and p38 MAPK-Mediated PI3K/AKT Activations. Cells. 2020; 9(7):1670. https://doi.org/10.3390/cells9071670

Chicago/Turabian Style

Kim, Ji-Eun, Hana Park, Ji-Eun Lee, and Tae-Cheon Kang. 2020. "Blockade of 67-kDa Laminin Receptor Facilitates AQP4 Down-Regulation and BBB Disruption via ERK1/2-and p38 MAPK-Mediated PI3K/AKT Activations" Cells 9, no. 7: 1670. https://doi.org/10.3390/cells9071670

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