ArticleNeurochemistry international2022
The interplay between MMP-12 and t-PA in the brain after ischemic stroke.
Article in Neurochemistry international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Neuroinflammatory Response to Postnatal Administration of Valproic Acid in Wistar Rats as a Mechanism for the Development of Autism Spectrum Disorders: The Role of Neutrophils.Brain sciences · 2026Article
- Fatty Acid-binding Protein 4 Exacerbates Blood-brain Barrier Disruption Through the JNK/c-Jun/MMP12 Pathway After Traumatic Brain Injury.Molecular neurobiology · 2025Article
- Implications of MMP-12 in the pathophysiology of ischaemic stroke.Stroke and vascular neurology · 2024Review
- The paradox of tPA in ischemic stroke: tPA knockdown following recanalization improves functional and histological outcomes.Experimental neurology · 2024Article
- Causal effect of serum matrix metalloproteinase levels on venous thromboembolism: a Mendelian randomization study.Epidemiology and health · 2024Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Tissue-type plasminogen activator (t-PA) expression is known to increase following transient focal cerebral ischemia and reperfusion. Previously, we reported downregulation of t-PA upon suppression of matrix metalloproteinase-12 (MMP-12), following transient focal cerebral ischemia and reperfusion. We now present data on the temporal expression of t-PA in the brain after transient ischemia, as well as the interaction between MMP-12 and t-PA, two proteases associated with the breakdown of the blood-brain barrier (BBB) and ischemic brain damage. We hypothesized that there might be reciprocal interactions between MMP-12 and t-PA in the brain after ischemic stroke. This hypothesis was tested using shRNA-mediated gene silencing and computational modeling. Suppression of t-PA following transient ischemia and reperfusion in rats attenuated MMP-12 expression in the brain. The overall effect of t-PA shRNA administration was to attenuate the degradation of BBB tight junction protein claudin-5, diminish BBB disruption, and reduce neuroinflammation by decreasing the expression of the microglia/macrophage pro-inflammatory M1 phenotype (CD68, iNOS, IL-1β, and TNFα). Reduced BBB disruption and subsequent lack of infiltration of macrophages (the main source of MMP-12 in the ischemic brain) could account for the decrease in MMP-12 expression after t-PA suppression. Computational modeling of in silico protein-protein interactions indicated that MMP-12 and t-PA may interact physically. Overall, our findings demonstrate that MMP-12 and t-PA interact directly or indirectly at multiple levels in the brain following an ischemic stroke. The present findings could be useful in the development of new pharmacotherapies for the treatment of stroke.
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Registered trials
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