Inflammation modulates expression of laminin in the central nervous system following ischemic injury

Abstract

BackgroundIschemic stroke induces neuronal death in the core of the infarct within a few hours and the secondary damage in the surrounding regions over a long period of time. Reduction of inflammation using pharmacological reagents has become a target of research for the treatment of stroke. Cyclooxygenase 2 (COX-2), a marker of inflammation, is induced during stroke and enhances inflammatory reactions through the release of enzymatic products, such as prostaglandin (PG) E2.MethodsWild-type (WT) and COX-2 knockout (COX-2KO) mice were subjected to middle cerebral artery occlusion (MCAO). Additionally, brain slices derived from these mice or brain microvascular endothelial cells (BMECs) were exposed to oxygen-glucose deprivation (OGD) conditions. The expression levels of extracellular matrix (ECM) proteins were assessed and correlated with the state of inflammation.ResultsWe found that components of the ECM, and specifically laminin, are transiently highly upregulated on endothelial cells after MCAO or OGD. This upregulation is not observed in COX-2KO mice or WT mice treated with COX-2 inhibitor, celecoxib, suggesting that COX-2 is associated with changes in the levels of laminins.ConclusionsTaken together, we report that transient ECM remodeling takes place early after stroke and suggest that this increase in ECM protein expression may constitute an effort to revascularize and oxygenate the tissue.

The role of TRPC6 in oxidative stress-induced podocyte ischemic injury

“…In this study, we found that TRPC6 expression was increased after renal ischemia reperfusion injury. In cultured human podocytes, OGD and reoxygenation treatment, a wellestablished model that mimics ischemic injury [18], enhanced Real-time PCR experiments suggest that TRPC6 siRNA significantly reduced the mRNA levels of TRPC6 but not TRPC1 and TRPC3 (n ¼ 3). Western blot analyses indicate that transfection with TRPC6 siRNA significantly reduced TRPC6 protein expression compared with the scrambled siRNA (n ¼ 3).…”

Regulation of the Immune System by Laminins

“…Overexpression of laminin α5 and α1 chains has been observed in inflammatory bowel disease [50]. Inflammation associated with ischemic injury increases laminin expression on endothelial cells in the central nervous system [51]. Finally, our laboratory previously demonstrated that laminin expression in the lymph node is differentially regulated following the induction of tolerance versus immunity [6].…”

Aberrant Production of Tenascin-C in Globoid Cell Leukodystrophy Alters Psychosine-Induced Microglial Functions

“…Differential production of ECM components has been reported in many CNS diseases, including Alzheimer disease (7), stroke (8), human immunodeficiency virus encephalitis (9), and multiple sclerosis (MS) (10). One widely studied implication of altered ECM composition includes dysregulation of cellular growth, differentiation and cell fate (11–14).…”