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

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Abstract

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.

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Acknowledgements

We appreciate the coworkers who participated in this study.

Funding

The authors acknowledge operating grant support from the National Natural Science Foundation of China (grant nos.: 82071331 and 81870942), Henan Provincial Key Research and Development and Promotion Special (grant no.: 232102311086), Henan Province Youth and Middle-aged Health Science and Technology Innovation Excellent Youth Talent Cultivation Project (grant no.: YQRC2023012), Henan Province Medical Science and Technology Research Plan Joint Construction Project (grant no.: LHGJ20230327), National Key Research and Development Program of China (grant no.: 2018YFC1312200), and from the Canadian Institutes of Health Research (Foundation grant 1049959).

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Authors and Affiliations

  1. Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Yang Liu, Lingxiao Qi, Zhe Li & Mengzhou Xue

  2. Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, China

    Yang Liu, Lingxiao Qi, Zhe Li & Mengzhou Xue

  3. Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

    V. Wee Yong

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YL searched the literature and drafted the manuscript. LXQ and ZL evaluated the literature. VWY and MX critically revised the manuscript. All authors contributed to the article and approved the submitted version.

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Liu, Y., Qi, L., Li, Z. et al. Crosstalk Between Matrix Metalloproteinases and Their Inducer EMMPRIN/CD147: a Promising Therapeutic Target for Intracerebral Hemorrhage. Transl. Stroke Res. (2023). https://doi.org/10.1007/s12975-023-01225-6

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  • DOI: https://doi.org/10.1007/s12975-023-01225-6

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