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基质金属蛋白酶与其诱导剂EMMPRIN/CD147之间的相互作用:脑出血的一个有前景的治疗靶点。

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

作者信息

Liu Yang, Qi Lingxiao, Li Zhe, Yong V Wee, Xue Mengzhou

机构信息

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

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

出版信息

Transl Stroke Res. 2025 Apr;16(2):557-567. doi: 10.1007/s12975-023-01225-6. Epub 2023 Dec 15.

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.

摘要

脑出血(ICH)的特征是脑血管完整性破坏,导致血肿扩大、水肿形成以及脑实质的物理损伤。原发性脑出血还会引发由氧化应激、免疫反应失调和蛋白水解导致的继发性脑损伤。在这种情况下,基质金属蛋白酶(MMPs)是一个普遍存在的超家族,由结构相关的锌依赖性内肽酶组成,能够降解细胞外基质的所有成分。它们破坏血脑屏障并促进神经炎症。重要的是,几种MMP成员在脑出血后上调,并且成员在脑出血的特定时期可能具有不同的功能。因此,MMPs的调节和功能比预期更复杂。细胞外基质金属蛋白酶诱导剂(EMMPRIN,CD147)是一种跨膜糖蛋白,可诱导MMPs的产生。在这篇综述中,我们系统地讨论了MMPs和EMMPRIN/CD147在脑出血中的生物学和功能以及它们之间复杂的相互作用。

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