Lysophosphatidic acid receptor, LPA6 , regulates endothelial blood-brain barrier function: Implication for hepatic encephalopathy

Biochemical and Biophysical Research Communications
Kayo MasagoTakao Shimizu

Abstract

Cerebral edema is a life-threatening neurological condition characterized by brain swelling due to the accumulation of excess fluid both intracellularly and extracellularly. Fulminant hepatic failure (FHF) develops cerebral edema by disrupting blood-brain barrier (BBB). However, the mechanisms by which mediator induces brain edema in FHF remain to be elucidated. Here, we assessed a linkage between brain edema and lysophosphatidic acid (LPA) signaling by utilizing an animal model of FHF and in vitro BBB model. Azoxymethane-treated mice developed FHF and hepatic encephalopathy, associated with higher autotaxin (ATX) activities in serum than controls. Using in vitro BBB model, LPA disrupted the structural integrity of tight junction proteins including claudin-5, occludin, and ZO-1. Furthermore, LPA decreased transendothelial electrical resistances in in vitro BBB model, and induced cell contraction in brain endothelial monolayer cultures, both being inhibited by a Rho-associated protein kinase inhibitor, Y-27632. The brain capillary endothelial cells predominantly expressed LPA6 mRNA, whose knockdown blocked the LPA-induced endothelial cell contraction. Taken together, the up-regulation of serum ATX in hepatic encephalopathy may a...Continue Reading

Citations

Mar 9, 2020·Metabolic Brain Disease·Ali SepehrinezhadRoger Williams
Feb 6, 2019·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
Jun 26, 2020·Frontiers in Cellular Neuroscience·Brock R PluimerZhen Zhao
Jan 5, 2021·Frontiers in Cellular Neuroscience·Ashwini HariharanThomas A Longden
Feb 3, 2021·Signal Transduction and Targeted Therapy·Luiz Henrique Medeiros GeraldoFlavia Regina Souza Lima
Oct 24, 2020·International Journal of Molecular Sciences·Anna Maria CzarneckaMagdalena Zielińska
Jun 15, 2021·European Journal of Medicinal Chemistry·Bhagyalalitha MeduriBijo Mathew

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