Crosstalk Between Matrix Metalloproteinases and Their Inducer EMMPRIN/CD147: a Promising Therapeutic Target for Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is characterized by the disruption of cerebrovascular integrity, resulting in hematoma enlargement, edema formation, and physical damage in the brain parenchyma. Primary ICH also leads to secondary brain injury contributed by oxidative stress, dysregulated immune responses, and proteolysis. In this context, matrix metalloproteinases (MMPs) represent a ubiquitous superfamily of structurally related zinc-dependent endopeptidases capable of degrading all components of the extracellular matrix. They disrupt the blood-brain barrier and promote neuroinflammation. Importantly, several MMP members are upregulated following ICH, and members may have different functions at specific periods in ICH. Hence, the modulation and function of MMPs are more complex than expected. Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that induces the production of MMPs. In this review, we systematically discuss the biology and functions of MMPs and EMMPRIN/CD147 in ICH and the complex crosstalk between them.