Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMPs) are a family of more than twenty secreted and cell-surface endopeptidases. Among them, MMP2, MMP3 and MMP9 are involved in blood-brain barrier injury and neuronal death after cerebral ischaemia. On the other hand, very little is known about the expression of the other secreted MMPs. Herein, we compared the global changes in MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12 and MMP13, and their endogenous inhibitors TIMP1 and TIMP2, both at the mRNA and protein levels, during the hyperacute (6 h), acute (24 h) and subacute (72 h) stages following transient focal cerebral ischaemia and treatment with recombinant tissue plasminogen activator (rtPA). We observed a significant increase in MMP1, MMP2, MMP9, MMP10, MMP13 and TIMP1 levels during the acute stage of reperfusion, which was further amplified during the subacute stage for MMP1, MMP2, MMP10 and TIMP1. In general, no change of MMP3, MMP7, MMP8, MMP12 and TIMP2 was observed. However, rtPA treatment induced a rapid increase in MMP1/TIMP2, MMP2/TIMP2, MMP8/TIMP2 and MMP9/TIMP2 ratios during the hyperacute stage of reperfusion compared to saline treatment, which may have potential implications in the early disruption of the blood-brain barrier after rtPA treatment.
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PMID:Analysis of the expression of nine secreted matrix metalloproteinases and their endogenous inhibitors in the brain of mice subjected to ischaemic stroke. 2467 55

Our study proposed to investigate the function of potassium voltage-gated channel sub-family Q member 1 opposite strand 1 (KCNQ1OT1) in cerebral ischemia-reperfusion (I/R) injury and the underlying mechanism. We constructed an oxygen-glucose-deprivation/reoxygenation (OGD/R) model using the primary cortical neurons to mimic the cerebral I/R injury in vitro. Small inference RNA (siRNA) was used to silencing KCNQ1OT1. Dual luciferase assay was conducted to verify the interaction between KCNQ1OT1 and miR-9 and interaction between miR-9 and MMP8. CCK8 assay and flow cytometry analysis were applied for determing the viability and apoptosis of neurons, accordingly. QPCR and Western blot were performed to determine the RNA and protein expression. Our outcomes revealed that the expression of KCNQ1OT1 in cultured neurons was notably enhanced after suffered to OGD/R. Knockdown of KCNQ1OT1 weakened OGD/R-induced injury in neurons. Moreover, depletion of KCNQ1OT1 lead to the up-regulation of miR-9 and down-regulation of MMP8. Dual luciferase target validation assays demonstrated that KCNQ1OT1 directly interact with miR-9 and MMP8 is a direct target of miR-9, suggesting that KCNQ1OT1/miR-9/MMP8 might constitute the competing endogenous RNA (ceRNA) mechanism. Knockdown of MMP8 or up-regulation of miR-9 also could weaken OGD/R-induced injury. Furthermore, cells co-transfected with si-KCNQ1OT1, miR-9 mimic and si-MMP8 could significantly abolish the injury on neurons caused by OGD/R. Taken together, our data manifested that KCNQ1OT1 possibly acts as a facilitator in cerebral I/R injury through modulating miR-9/MMP8 axis as a ceRNA.
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PMID:LncRNA KCNQ1OT1 contributes to oxygen-glucose-deprivation/reoxygenation-induced injury via sponging miR-9 in cultured neurons to regulate MMP8. 3183 24