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基质金属蛋白酶及其抑制剂在上皮分化、血管疾病、子宫内膜异位症和眼部纤维化翼状胬肉发病机制中的作用

Matrix Metalloproteinases and Their Inhibitors in the Pathogenesis of Epithelial Differentiation, Vascular Disease, Endometriosis, and Ocular Fibrotic Pterygium.

作者信息

Park Jun-Young, Choi Yeonwoo, Kim Hee-Do, Kuo Han-Hsi, Chang Yu-Chan, Kim Cheorl-Ho

机构信息

Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Environmental Diseases Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon 34141, Republic of Korea.

出版信息

Int J Mol Sci. 2025 Jun 10;26(12):5553. doi: 10.3390/ijms26125553.

Abstract

Matrix metalloproteinases (MMPs) are key enzymes involved in the remodeling of the extracellular matrix (ECM) through the degradation of its components in a controlled endoproteolytic manner. Beyond ECM degradation, MMPs also target plasma membrane proteins implicated in signaling cascades and the progression of disease. Structurally, the catalytic function of MMPs is dependent on metal ions such as Zn. ECM remodeling by MMPs supports processes including tissue growth, morphogenesis, elongation, and adaptation to environmental changes occurring under both physiological and pathological conditions. These activities are subject to tight regulation by cellular MMP enzymes. While the current body of research has primarily centered on the functions of MMPs and their roles in cancer biology, knowledge of their involvement in vascular disease, endometriosis, fibrotic eye disease, epithelial cell differentiation, and the actions of MMP inhibitors remains comparatively sparse. This review explores the roles of MMPs in vascular disease and endometriosis, particularly as they relate to the ectopic growth of endometrial tissue. In addition, we summarize evidence regarding their contributions to disease mechanisms, with a focus on pathological progression. Due to their significant therapeutic promise in a variety of human diseases, advancing our understanding of MMP biology is likely to facilitate progress in clinical application and the development of novel interventions. This review also evaluates advances in the development and therapeutic potential of MMP inhibitors.

摘要

基质金属蛋白酶(MMPs)是一类关键酶,通过以内切蛋白水解的可控方式降解细胞外基质(ECM)的成分,参与ECM的重塑过程。除了ECM降解外,MMPs还作用于参与信号级联反应和疾病进展的质膜蛋白。在结构上,MMPs的催化功能依赖于锌等金属离子。MMPs介导的ECM重塑支持包括组织生长、形态发生、伸长以及对生理和病理条件下发生的环境变化的适应等过程。这些活动受到细胞内MMP酶的严格调控。虽然目前的研究主要集中在MMPs的功能及其在癌症生物学中的作用,但它们在血管疾病、子宫内膜异位症、纤维化眼病、上皮细胞分化以及MMP抑制剂的作用方面的相关知识仍然相对较少。本综述探讨了MMPs在血管疾病和子宫内膜异位症中的作用,特别是它们与子宫内膜组织异位生长的关系。此外,我们总结了关于它们对疾病机制贡献的证据,重点关注病理进展。由于它们在多种人类疾病中具有显著的治疗前景,加深我们对MMP生物学的理解可能会促进临床应用的进展和新型干预措施的开发。本综述还评估了MMP抑制剂的开发进展及其治疗潜力。

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