Urokinase-Type Plasminogen Activator Receptor Modulates Epileptogenesis in Mouse Model of Temporal Lobe Epilepsy.
http://www.ncbi.nlm.nih.gov/pubmed/23263886
Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland
Abstract
Mutation in Plaur gene encoding urokinase-type plasminogen activator receptor (uPAR) results in epilepsy and autistic phenotype in mice.
In humans, a single nucleotide polymorphism in PLAUR gene represents a risk for autism spectrum disorders.
Importantly, the expression of uPAR is elevated in the brain after various epileptogenic insults like traumatic brain injury and status epilepticus.
So far, the consequences of altered uPAR expression on brain networks are poorly known.
We tested a hypothesis that uPAR regulates post-injury neuronal reorganization and consequent functional outcome, particularly epileptogenesis.
Epileptogenesis was induced by intrahippocampal injection of kainate in adult male wild type (Wt) or uPAR knockout (uPAR-/-) mice, and animals were monitored with continuous (24/7) video-electroencephalogram for 30Â days. The severity of status epilepticus did not differ between the genotypes.
The spontaneous electrographic seizures which developed were, however, longer and their behavioral manifestations were more severe in uPAR-/- than Wt mice. The more severe epilepsy phenotype in uPAR-/- mice was associated with delayed but augmented inflammatory response and more severe neurodegeneration in the hippocampus.
Also, the distribution of newly born cells in the dentate gyrus was more scattered, and the recovery of hippocampal blood vessel length from status epilepticus-induced damage was compromised in uPAR-/- mice as compared to Wt mice.
Our data demonstrate that a deficiency in uPAR represents a mechanisms which results in the development of a more severe epilepsy phenotype and progressive brain pathology after status epilepticus. We suggest that uPAR represents a rational target for disease-modifying treatments after epileptogenic brain insults.
——————————————
The urokinase-receptor in infectious diseases.
http://www.ncbi.nlm.nih.gov/pubmed/23042001
Department of Cellular and Molecular Biology and Pathology, University Federico II, Naples, Italy.
Abstract
Cell migration through the extracellular matrix (ECM) or endothelial cells is a basic process in several physiological and pathological events, including the immune host response to pathogens, both in the case of innate and adaptive immunity.
The urokinase-type plasminogen activator (uPA) receptor (uPAR) is a GPI-anchored cell-surface receptor largely expressed on most of leukocytes, including monocytes/macrophages, granulocytes, immature dendritic cells.
uPAR has been detected also in soluble and cleaved forms, which are increased in several pathologies. uPAR focuses the proteolytic activity of its ligand, the serine-protease uPA, on the cell membrane, thus promoting localized plasminogen activation and allowing the cell to degrade surrounding ECM and to move across physical barriers.
However, the discovery that uPAR can bind with high affinity a component of the ECM, vitronectin (VN), and associates to cell surface molecules to activate signalling pathways inside the cells, largely expanded the role that uPAR can play in cell proliferation/survival and adhesion/migration, which are crucial events for an efficient immune response to infectious agents.
This review is focused on the expression and possible functions of the various forms of uPAR in infectious diseases.
