EMMPRIN/CD147 plays a detrimental role in clinical and experimental ischemic stroke

Abstract

Background: Ischemic stroke is a devastating disease, often resulting in death or permanent neurological deficits. EMMPRIN/CD147 is a plasma membrane protein that induces the production of matrix metalloproteinases (MMPs), which contribute to secondary damage after stroke by disrupting the blood brain barrier (BBB) and facilitating peripheral leukocyte infiltration into the brain. Results: CD147 surface expression increased significantly after stroke on infiltrating leukocytes, astrocytes and endothelial cells, but not on resident microglia. Inhibition of CD147 reduced MMP levels, decreased ischemic damage, and improved functional, cognitive and histological outcomes after experimental ischemic stroke in both young and aged mice. In stroke patients, high levels of serum CD147 24 hours after stroke predicted poor functional outcome at 12 months. Brain CD147 levels were correlated with MMP-9 and secondary hemorrhage in post-mortem samples from stroke patients. Conclusions: Acute inhibition of CD147 decreases levels of MMP-9, limits tissue loss, and improve long-term cognitive outcomes following experimental stroke in aged mice. High serum CD147 correlate with poor outcomes in stroke patients. This study identifies CD147 as a novel, clinically relevant target in ischemic stroke.

The hallmarks of COVID-19 disease

“…Therefore, the functional interaction between TMPRSS2 and furin is a key factor in determining the level of S protein priming. Other host proteins-such as heat shock protein family A (hsp70) member 5 (HSPA5, also known as GRP78) [43] and CD147 (an inducer of matrix metalloproteinase synthesis) [44]-may play an alternative or synergistic role in mediating SARS-CoV-2 invasion, although their structural basis is still unknown. It also remains to be seen whether ACE2 expression in other tissues, such as the gastrointestinal tract, kidney, and heart, has similar functions as in the lung.…”

Astrocytes in the regulation of cerebrovascular functions

“…Reactive astrocytes also secrete inflammatory cytokines (e.g., IL‐15), which recruit CD8 + T cells and natural killer cells and thereby aggravate the brain lesions (Li et al, 2017; Shi et al, 2020). A recent study using the middle cerebral artery occlusion (MCAO) model suggested that CD147 (EMMPRIN/basigin), an extracellular MMP‐inducer that induces MMP activity and promotes leukocyte extravasation and inflammation (Agrawal & Yong, 2011) is produced by astrocytes during stroke (Patrizz et al, 2020). With regard to the astrocyte endfeet repertoire, Aqp4 expression increases during edema and ischemia.…”

Clemastine promotes recovery of neural function and suppresses neuronal apoptosis by restoring balance of pro-inflammatory mediators in an experimental model of intracerebral hemorrhage

“…The release of inflammatory cytokines comes mainly from microglial cells and some researchers have reported that the numbers of cells reached the peak value at 3 days post injury in ICH animal models 23 , 24 . Microglia can be triggered to release pro-inflammatory mediators that are toxic to neurons 25 .…”